The problem of HIV internationally has many wide ranging impacts on people, communities and countries' development. In the last decade antiretroviral (ARV) treatment has emerged as the major scientific-technical solution, albeit a costly one. Access to ARV treatment is of vital importance across Africa and around the world. Resources for HIV treatment, care and support are transferred globally on a massive scale. However, how such programmes operate ‘on the ground' in different contexts is still unclear. This research contributes to understanding the experience of the people who access such treatment programmes in different contexts. This research focuses on this gap, exploring how treatment programmes are experienced, how the availability of treatment impacts both on people's experience of being HIV+ and how the availability of treatment may also change perceptions of what it means to be HIV+, both individually and at a societal level. This research focuses on the lives and experiences, particularly the treatment experiences, of people living with HIV in peri-urban Gambia. Low prevalence countries such as The Gambia can provide a compelling example of the ways in which meanings and understandings of HIV are created. Here, entering a field of health pluralism and fluid knowledge creation around HIV-infection, came large scale actors providing a high-profile ARV treatment programme through clinic-based medicine, and an effective de-pluralisation of the medical field in relation to HIV, inviting scrutiny of how such knowledge relations and differences are experienced. Although not anticipated at the outset of the research, in parallel the Gambia has become the locus of a major, politically-backed, ‘alternative' AIDS treatment programme. This has thrown the personal and societal meanings of HIV into a new and sensitive context, compelling research attention into how knowledge, status and meanings around HIV are negotiated, and how people make choices amongst different treatment options.

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.

Thesis ( MPH ) -- University of Limpopo (Medunsa Campus), 2013. / Background and introduction Disclosure of HIV sero-status is critical in the control of the spread of HIV and research. To better understand the factors influencing disclosure will enhance the development of prevention interventions and ultimately lead to better control of the spread of the disease. However literature shows that the rates of disclosure are generally low and vary substantially in different populations. Study purpose To determine the prevalence, reasons for disclosure, partner reaction to disclosure, and intentions of disclosure to sexual partners among HIV positive adults receiving antiretroviral treatment. Study design Cross sectional survey was conducted with 400 adult patients aged 18 years and above, who receive ART, and have known their HIV status for six more than six months. Structured close ended self-administered questionnaire was used to collect data. The study participants were recruited from a wellness clinic of an academic hospital in the City of Johannesburg, Gauteng province between October and November 2012. Descriptive and inferential statistics were performed using STATA 10 for analysis. Pearson X2 tests were used to determine variables associated with disclosure. Results A total of 400 HIV positive adults participated in the survey. There were slightly more female (n=229, 57%) than male (n=171, 43%), the mean age of participants was 39.9 years, (range 18-80 years). Almost half (n=176, 46%) had known of their HIV diagnosis for more than 5 years. High proportion (n=293, 73%) were sexually active three months prior to the survey, (n=250, 63%) knew their partner’s HIV status, more than a third (n=145, 36.3%) had more than one sexual partner, (n=263, 73.5%) reported condom use, (n=261, 75%) disclosed to their partners. Gender, discussing HIV testing with sexual partner, knowing partner’s HIV status, and living with partner were significantly associated with disclosure. iv The most common cited reasons for disclosure were that they needed to protect their partner from being infected with HIV, and needed support from their partner. Partner reactions to disclosure included support, shock, and denial of the test results, blame, abandonment, violence, anger, and divorce. The most cited reasons for nondisclosure were concerns that the partner might leave, partner might be afraid of catching HIV, partner might think they were unfaithful, partner might get angry, partner might hurt them physically and that partner might stop financial support. Conclusion The study concludes that the prevalence of disclosure to sexual partners among sexually active adults was high and that most respondents disclosed immediately after they were diagnosed with HIV. However, disclosure to multiple sexual partners was lower as compared to disclosure to the steady partner. Respondents disclosed to protect the partner from HIV infection and to receive support. Nondisclosure was mainly used to protect self from negative reactions from the partner. Recommendations Researchers and health care providers needs to take cognisant of the risk sexual behaviour an low condom use among HIV positive adults receiving ART. Secondary prevention efforts targeting risky sexual behaviour among HIV-positive persons need to receive greater attention.

The human immunodeficiency virus type 1 (HIV-1) uses a mechanism of genetic recoding known as programmed ribosomal frameshifting to translate the proteins encoded by the pol gene. The pol gene overlaps the preceding gag gene in the -1 reading frame relative to gag. It contains neither a start codon nor an internal ribosome entry site (IRES) to initiate translation of its proteins. Rather the host ribosomes are forced to pause due to tension placed on the mRNA when they encounter a specific secondary structural element in the mRNA. This tension is relieved by disruption of the contacts between the mRNA codons and tRNA anticodons at a �slippery� sequence within the ribosomal decoding centre. Re-pairing of the tRNAs occurs in the new -1 frame after movement of the mRNA backwards by one nucleotide, allowing the ribosome to translate the pol gene as a Gag-Pol polyprotein. A change in ratio of Gag to Gag-Pol proteins affects viral assembly, and most significantly dramatically reduces viral infectivity. The prevailing model for the mechanism of -1 frameshifting has focussed on a pre-translocational event, where slippage occurs when the slippery sequence is within the ribosomal A and P sites. This model precludes a contribution from the codon immediately downstream of the slippery sequence leading into the secondary structural element. I have termed this the �intercodon�. Often at frameshifting sites it is a termination codon, whereas in HIV-1 it is a glycine codon, GGG. When the intercodon within the frameshift element was changed from the wild-type GGG to a termination codon UGA, the efficiency of frameshifting decreased 3-4-fold in an in vivo assay in cultured human cells. This result mimicked previous data in the group within bacterial cells and cultured monkey COS-7 cells. Changing the first nucleotide of the intercodon to each of the three other bases altered frameshifting to varying degrees, but not following expected patterns for base stacking effects. Such a result would support a post-translocational model for -1 frameshifting. It suggested that the intercodon might be within the ribosomal A site before frameshifting, and that the slippery sequence was therefore within the P and E sites. This was investigated by modulating the expression of decoding factors for the intercodon - the release factor eRF1 and cognate suppressor tRNAs when it was either of the UGA or UAG termination codons, and tRNA[Gly] for the native GGG glycine codon. These were predicted to affect frameshifting only if slippage were occurring when the ribosomal elongation cycle was in the post-translocational state. Overexpression of tRNA[Gly] gave inconsistent effects on frameshifting in vivo, implying that its concentration may not be limiting within the cell. When eRF1 was overexpressed or depleted by RNAi, significant functional effects of decreased or increased stop codon readthrough respectively were documented. Expression of suppressor tRNAs increased readthrough markedly in a stop codon-specific manner. These altered levels of eRF1 expression were able to modulate the +1 frameshifting efficiency of the human antizyme gene. Overexpression of eRF1 caused significant reduction of frameshifting of the HIV-1 element with the UAG or UGA intercodon. Depletion of the protein by contrast had unexplained global effects on HIV-1 frameshifting. Suppressor tRNAs increased frameshifting efficiency at the UAG or UGA specifically in a cognate manner. These results strongly indicate that a post-translocational mechanism of frameshifting is used to translate the HIV-1 Gag-Pol protein. A new model (�almost� post-translocational) has been proposed with -1 frameshifting occurring for 1 in 10 or 20 ribosomal passages during the end stages of translocation, because of opposing forces generated by translocation and by resistance to unwinding of the secondary structural element. With translocation still incomplete the slippery sequence is partially within the E and P sites, and the intercodon partially within the A site. The nature of the intercodon influences frameshifting efficiency because of how effectively the particular decoding factor is able to bind to the partially translocated intercodon and maintain the normal reading frame.

HIV-associated lipodystrophy (HIVLD) syndrome is a condition comprising abnormalities in distribution of body fat and metabolism of lipids and glucose that arises in HIV-infected patients on long-term antiretroviral therapy. This thesis describes clinical research into aspects of the natural history and treatment of HIVLD, as well as molecular research into its pathogenesis centred on subcutaneous adipose tissue. Results demonstrate HIVLD to be a treatment-induced syndrome characterised by initial gains in body fat followed by selective, progressive loss of limb fat. Exposure to thymidineanalogue nucleoside reverse transcriptase inhibitors (tNRTI) induces lipoatrophy through mitochondrial dysfunction of which inhibition of mitochondrial RNA expression, rather than mitochondrial DNA depletion, is an early feature. Mitochondrial dysfunction is associated with decreases in expression of peroxisome proliferatoractivated receptor gamma (PPAR??), an adipocyte transcription factor, which helps explain how tNRTI exposure leads to the loss of adipocyte function. Once established, lipoatrophy is characterised by mitochondrial DNA depletion, although this depletion occurs throughout the mitochondrial genome, suggesting an underlying cause other than inhibition of DNA polymerase gamma. HIVLD is a difficult syndrome to treat. Lipoatrophy is resistant to treatment with rosiglitazone, an agonist of PPAR??, which is ineffective in the setting of ongoing tNRTI therapy and mitochondrial dysfunction. Dyslipidaemia is also difficult to treat as use of pravastatin in the setting of ongoing exposure to protease inhibitors results in only modest declines in fasting cholesterol concentrations. Gains in central fat, such as that seen in patients with buffalo hump, are associated with insulin resistance and diabetes, but only occur in a relatively small percentage of treated patients, suggesting a role for genetic factors in its development. Use of strategies such as avoidance of tNRTI in firstline ART, genetic screening to identify those at risk of toxicities and targeted selection of interventions in subgroups of affected patients, may help prevent this syndrome occurring and better treat those patients in which it has already occurred.

The death toll from AIDS continues to rise in the United States. As of May 1, 1995, 441,528 cases of AIDS had been recorded in the U. S. One of the most powerful ways to control the spread of this disease is prevention education. In 1988, Oregon passed OAR 581-22-412 requiring implementation of HIV/AIDS education as a part of a comprehensive health education program throughout grade levels K-12. The Oregon Department of Education and the Oregon Health Division produced a curriculum and implemented a statewide inservice program in 1988. There has been no uniform statewide training since then, nor have implementation practices been monitored consistently. Sixth grade is a pivotal time in childhood when children are passing through puberty into adolescence. Sixth grade may be placed in a middle school with a health specialist, or in an elementary school with no health teacher. This grade may be the final opportunity for intervening before students adopt behavior patterns which may lead to HIV/AIDS. The purposes for this study were twofold. The first was to determine the extent to which Oregon sixth-grade teachers were implementing HIV/AIDS education. The second was to discover what factors might predict whether a sixth-grade teacher would be an implementer. A random stratified sample of 400 was drawn from the population of 1,333 sixth-grade teachers employed during 1993-1994. These teachers received a written questionnaire. Three-hundred and six teachers returned surveys. One-hundred and twenty of the subjects met the definition for implementer and 48 were determined to be non-implementers. The remaining 138 did not supply enough information to be categorized but their responses were used where applicable. Null hypotheses were tested using the chi-square and Mann-Whitney U statistics. Significant factors were whether teachers had some training and having had training in characteristics of HIV infection, low-risk behaviors leading to HIV infection, prevention behaviors, infection control, and social implications of AIDS. Regression analysis was employed to determine factors which predict that a teacher will be an implementer. Significant factors were a) having had inservice in low-risk behaviors, b) teaching in a self-contained classroom, c) and not defining oneself as politically conservative. / Graduation date: 1996

hesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2007.

Thesis (Ph.D.)--Georgia State University, 2005. / Title from title screen. Roger Bakeman, committee chair; James Emshoff, John Peterson, Gabriel Kuperminc, committee members. Electronic text (100 p.) : digital, PDF file. Description based on contents viewed Apr. 24, 2007. Includes bibliographical references (p. 90-100).

Introduction: HIV is a serious problem in Namibia, 13.1% of the adult population is HIV-positive or is a carrier of AIDS. This is one of the highest numbers in the world. HIV is passed from mother to child during pregnancy, during labour or through breast milk. 18.8 % of the pregnant mothers in Namibia who is in contact with the maternity welfare have HIV. Aim: The aim of the study was to describe nurses’ counseling to mothers to prevent mother to child transmission of HIV through breastfeeding. Method: Eight nurses working with PMTCT of HIV were interviewed in Namibia. The interviews were transcribed and a content analysis was made. 18 sub-categories and seven categories were found. Findings: It is important that nurses provide individual counseling, are supportive and motivate the mothers. Poverty is an obstacle for the mothers, stigmatization occurs and cultural differences can have influence on the mothers. It is also important that nurses are updated in counseling and PMTCT. Conclusion: Nurses should provide mothers with the correct information in a pedagogical way. Nurses need to be aware of obstacles for the mothers and their families to be able to meet their different demands. Men are not involved in PMTCT-counseling and nurses think that partner involvement would benefit PMTCT of HIV.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2008. / Vita. Includes bibliographical references.