PhD, Faculty of Health Sciences, University of the Witwatersrand / The aim of the study was to explore the practice of antiretroviral (ARV) therapy services, specifically regarding the patients’ issues and experiences, as well as the experiences of the health care providers rendering these services. Qualitative research methods were used, including a metasynthesis of qualitative research articles on human immunodeficiency virus (HIV) positive patients on ARV therapy, and phenomenological methods of inquiry. The study objectives were to conduct a metasynthesis of qualitative research on HIV-positive people on ARV therapy; to investigate the experiences of HIV-positive people who are on ARV therapy; to identify the constraints faced by HIV-positive people receiving ARV therapy; and to explore adherence to ARV therapy. The study was conducted in eThekwini district in KwaZulu Natal (KZN) province. The district was chosen considering the number of clinics rolling out ARV therapy. Three institutions initiating ARV therapy participated in the study; one urban, one semi-urban and one rural clinic, to ensure representation of each type. Participants were recruited from two initiating hospitals and one Community Health Centre providing ARV therapy. The metasynthesis revealed a shared set of four themes viz.: 1. Acceptance of, and coping with, HIV positive status 2. Social support and disclosure 3. Experiences and beliefs about HIV medication and health care 4. Provider relationships and health system factors Qualitative analyses of interviews with clients indicated their experiences and concerns, and were summarized in these themes: 1. Life before and after knowing HIV status 2. Initiating and continuing ARV therapy 3. Adherence to, and side effects of, the ARV therapy treatment 4. Social support for people on ARV treatment vi 5. Positive outcomes of being on ARV treatment 6. Improving access to ARV treatment services Analyses of in-depth interviews with health care providers specified their experiences, and were categorized into three themes viz.: 1. Establishing and maintaining a good client-provider relationship 2. Facilitators of and adherence to ARV treatment 3. Barriers to access to treatment

This study is one of the only investigations to examine the complex inter-relationships between immune status, cognitive functioning, and disease progression in school-aged, perinatally infected, HIV+ children on HAART over time and is the first to conduct long-term follow-up assessments beyond one year after initiating HAART. Previous research has shown that HIV+ children on HAART show stability in cognitive functioning for up to one year. The current study investigated cognitive functioning, as measured by the Wechsler Intelligence Scale for Children -III, as a function of immune functioning and disease progression over time in this sample. Overall, results showed that PIQ scores remained stable over the three time points. However, further analyses demonstrated that poorer immune status, as measured by CD4% <25, at the first time point significantly predicted lower Performance IQ (PIQ)scores and PIQ subtest scores at the third time point, even after controlling for covariates. Similarly, additional analyses revealed that PIQ scores significantly declined over time as a function of CD4% category at the first time point. Finally, scores on the PIQ, Verbal IQ (VIQ), Coding, Picture Arrangement, Symbol Search, and Arithmetic at the first time point were all significant predictors of more advanced disease progression, as measured by CDC C classification at follow-up. The clinical relevance of this study and recommendations for future research in this area are discussed

Introdução: A partir da segunda metade da década de noventa, a oferta de tratamento com a Terapia Antiretroviral de Alta Potência contribuiu para a redução da mortalidade de pessoas vivendo com aids nos locais com acesso universal a medicação. Porém, a introdução de procedimentos efetivos tem sido apontada como associada a desigualdades em saúde, quando fatores sociais dificultam o acesso e a aderência ao tratamento. Objetivo: Descrever a evolução temporal da mortalidade nos bairros de Campinas, verificando se houve declínio após a disponibilização da terapêutica antirretroviral de alta potência em 1997 e se este declínio foi homogêneo entre três agregados de áreas da cidade, ou se foi de algum modo associada com a condição socioeconômica das mesmas. Métodos: Foram avaliadas as taxas de mortalidade por aids em bairros de Campinas, São Paulo, de 1996 a 2012, a fim de testar sua associação com o status socioeconômico da área de residência após o início da oferta universal e sem custo de Terapia Antiretroviral de Alta Potência. Foram calculadas as taxas de mortalidade anuais por aids, ajustadas por sexo e faixa etária, com base em informações oficiais de população e mortalidade. Foi estimada a tendência de declínio da mortalidade por aids, usando o procedimento de auto-regressão de Prais- Winsten para séries temporais. A taxa de declínio anual nos três agregados de bairros da cidade foi comparada segundo índices socioeconômicos estimados para o Índice de Condições de Vida. Resultados: A mortalidade por aids ajustada por sexo e idade em Campinas caiu de 13,6 óbitos/100.000 habitantes em 1996 para 4,6 óbitos /100.000 habitantes em 2012. O decréscimo anual foi de 5,5 por cento (Intervalo de Confiança 95 por cento 3,3 por cento -7,5 por cento ). Não foram observadas diferenças significantes de mortalidade (magnitude e taxa de redução) entre as áreas de moradia. Na faixa etária de adultos (20 a 49 anos), houve menor queda da mortalidade no sexo feminino, principalmente na área de pior status socioeconômico. Conclusões: O programa de tratamento para as pessoas com aids foi efetivo para a redução global da mortalidade devida à doença na cidade de Campinas. A redução de mortalidade foi homogênea entre as áreas, o que é compatível com a hipótese de redução das desigualdades em saúde. Porém, a menor redução na mortalidade de mulheres, na faixa etária de adultos, principalmente na região de pior condição socioeconômica, aponta a persistência de desigualdades sociais em saúde. / Introduction: Since the second half of the 1990s, the provision of highly active antiretroviral therapy (HAART) contributed to the reduction in mortality of people living with AIDS in places with universal access to medication. However, the introduction of effective interventions has been identified as associated with health inequalities, when social factors hinder the access and adherence to treatment. Objective: to describe trends of mortality in the districts of Campinas, checking if there was decline after the release of the HAART in 1997 and if this decline was homogeneous among the three aggregate areas of the city, or was somehow associated with their socioeconomic status. Methods: We assessed AIDS mortality in neighborhoods of Campinas, São Paulo, from 1996 to 2012 in order to compare differences among areas of residence after the introduction of universal, free-of-cost provision of HAART. We estimated annual death rates by AIDS, as adjusted for sex and age, based on official information from population and mortality. The annual percent change of AIDS mortality was calculated using the procedure of Prais-Winsten for auto-regression of time series. We assessed differences of the annual percent change between the three clusters of neighborhoods; their socioeconomic status was informed by a socioeconomic index assessed by local health authorities. Results: The adjusted death rate by AIDS in Campinas reduced from 13.6 deaths/100,000 inhabitants in 1996 to 4.6 deaths/100,000 inhabitants in 2012. The annual percent change was 5.5 per cent (95 per cent Confidence Interval 3.3 per cent -7.5 per cent ). No significant differences of mortality (magnitude and annual percent change) among the living areas was observed. In the age group of adults (20-49 years old), a lower decrease of mortality in women was observed, especially in the area of lower socioeconomic status. Conclusions: The program of treatment for people with AIDS was effective in the city of Campinas, as refers to the overall reduction of mortality due to the disease. This reduction was homogeneous among the areas, which is consistent with the hypothesis of a reduction of inequalities in health. However, the lower reduction in mortality in women in the age group of adults, especially in the region of lower socioeconomic status, indicates the persistence of social inequalities in health.

Human immunodeficiency virus still remains the leading cause of death globally including women of child-bearing age. The rate of AIDS-related death has significantly declined since the introduction of antiretroviral treatment and other non-medical interventions such as the distribution and use of condoms. The introduction of antiretroviral treatment has however led to insulin resistance amongst users. Clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated nuclease 9 (Cas) has been used to knockout NFκB to understand the pathway at which antiretroviral treatment causes insulin resistance. Heteroduplex mobility assay has shown that CRISPR-Cas9 knock out the gene of interest. These results have played a foundation in understanding how CRISPR-Cas9 can be integrated and utilized in medical research. / Dissertation (MSc (Chemical Pathology))--University of Pretoria, 2020. / National Research Foundation (NRF) / Chemical Pathology / MSc (Chemical Pathology) / Restricted

Magister Psychologiae - MPsych / The aim of this study was to explore how HIV positive people understand and describe their experience of taking antiretroviral treatment consistently in a strictly organised regimen. Eight participants were recruited from Ikhwezi Clinic. The participants were interviewed using an in depth interview guide. A Phenomenological data analysis was employed through which six themes emerged. The themes are forgetting and memory aids, fitting treatment into daily routine, belief in effectiveness of medication, experiences of side effects, disclosure and social support and relationship with the health care provider. The health belief model and the self-efficacy theory were applied in the study. These theories helped to understand that the decision to take treatment is not only based on the individual experiences and beliefs but the interaction with the social and environmental factors as well. Family, community and health care factors are all interconnected and play a vital role in the decision to commence and continue with HAART. The study revealed that PLWHA can adhere to antiretroviral medication if they believe in the benefits of doing so. Furthermore it became clear that experiences of men and women differ when it comes to HAART. The involvement of the inlaws as experienced by the women in this study had a negative influence in the participants' adherence routine. Further studies are needed to explore the influence of culture in decision making by women with regards to their health.

Bestimmung der Prävalenz medikamentenresistenter HIV-Infektionen bei therapienaiven Patienten in der Viktoriasee-Region in Tansania Seitdem HIV im Jahr 1983 als Ursache des „acquired immundeficiency syndrome“ (AIDS) isoliert wurde, hat sich viel in der Therapie dieser Infektion getan. Trotzdem handelt es sich um eine Erkrankung, welche bisher nicht geheilt werden kann. Da der weitaus größere Anteil der betroffenen Menschen in strukturschwachen Ländern lebt, ist die größte Herausforderung, eine flächendeckende Therapie weltweit zu etablieren und diese für jeden zugänglich zu machen. Aufgrund der hohen Mutationsrate des HI-Virus, kommt es zur schnellen Resistenzentwicklung. In strukturschwachen Ländern wie Tansania ist eine Resistenztestung vor Therapiebeginn aktuell aufgrund fehlender Infrastruktur sowie geringer finanzieller Mittel nicht denkbar. Deshalb wird nach WHO-Empfehlung eine standardisierte Dreifachkombination, in der Regel Tenofovir, Lamivudin und Efavirenz, angewendet, ohne vorher eine Resistenztestung vorzunehmen. In regelmäßigen Nachuntersuchungen wird anhand von Viruslast und CD4-Zahl der Erfolg der begonnenen Therapie gemessen und nur bei einem Versagen dieser eine Umstellung vorgenommen. Bereits im Jahr 2011 wurde von unserer Arbeitsgruppe (Kasang, Kalluvya et al.) nachgewiesen, dass eine deutlich höhere Prävalenz für Primärresistenzen von HI-Viren gegenüber antiretroviraler Therapie bestand, als zuvor angenommen. Betrachtet wurden dabei alle Patienten, welche neu als HIV-positiv getestet wurden und nun therapiert werden sollten. Neu war, dass auch ältere Patienten (>25 Jahre) mit einbezogen wurden. Aufgrund der hohen Prävalenz an Primärresistenzen (19%) nahm man an, dass durch antiretrovirale Therapie entstandene resistente Viren zwischen Partnern direkt übertragen werden können. In der vorliegenden Arbeit sollte durch die Untersuchung einer größeren Patientengruppe dieser These nachgegangen werden. Untersucht wurde das Plasma von 114 Patienten (> 25 Jahre), welche unmittelbar vor dem Start einer antiretroviralen Therapie standen und bisher therapienaiv waren. Zur Bestimmung von möglicherweise vorliegenden Resistenzen erfolgte im S3-Labor zunächst die Isolierung der Virus-RNA aus dem Plasma. Diese wurde anschließend in DNA umschrieben, amplifiziert, aufgereinigt und sequenziert. Die Sequenzen wurden online durch die „HIV DRUG RESISTANCE DATABASE“ der Stanford University im Hinblick auf den Subtyp der reversen Transkriptase (RT), der Protease sowie auf Resistenzen gegenüber den gängigen aniretroviralen Medikamenten analysiert mit folgenden Ergebnissen: 1. Die Prävalenz für eine Primärresistenz gegenüber antiretroviralen Medikamenten betrug 21,5 % 2. Die Medikamente der Triple-Therapie waren in der untersuchten Gruppe mit einer Prävalenz von 10,53 % betroffen. 3. Diese Ergebnisse sind besorgniserregend und bestätigen die von Kasang, Kalluvya et al. aufgestellte These Für den weitaus größeren Teil der untersuchten Patienten wäre jedoch die Triple-Therapie ohne kostspielige und aufwendige Resistenztestung ausreichend gewesen. Vorderstes Ziel bleibt somit die finanziellen Ressourcen weiterhin Zugänglichkeit der medikamentösen Behandlung zu nutzen, da dies die beste Methode ist, die Ausbreitung dieser Pandemie einzudämmen. Dennoch werden in den nächsten Jahren weiterhin Untersuchungen mit noch größeren Patientenzahlen nötig sein, um die Wirksamkeit des aktuellen Therapieregimes ständig zu überprüfen und gegebenenfalls eine Anpassung vorzunehmen. / Determining the prevalence of drug-resistant HIV infections in treatment-naive patients in the Lake Victoria region of Tanzania Since HIV was identified as the cause of AIDS, there has been significant progress on the therapy of this disease although there is no cure. Most frequently those affected live in economically underdeveloped countries. Against this backdrop, the challenge is to establish a comprehensive therapy worldwide and make it available for everyone. Due to the high mutation rate of the HI virus, resistance develops quickly. In structurally weak countries such as Tanzania, resistance testing before the start of therapy is currently inconceivable due to the lack of infrastructure and low financial resources. Therefore, according to WHO recommendations, a standardised triple combination, usually tenofovir, lamivudine and efavirenz, is used without prior resistance testing. In regular follow-up examinations, the success of the therapy started is measured on the basis of viral load and CD4 count, and a change is only made if this fails. As early as 2011, our research group (Kasang, Kalluvya et al.) demonstrated that there was a significantly higher prevalence of primary resistance of HI viruses to antiretroviral therapy than previously assumed. All patients who were newly tested as HIV-positive, and were now to be treated, were considered. What was new was that older patients (>25 years) were also included. Due to the high prevalence of primary resistance (19%), it was assumed that resistant viruses resulting from antiretroviral therapy can be transmitted directly between partners. In the present study, this hypothesis was investigated by examining a larger group of patients. The plasma of 114 patients (> 25 years) who were about to start antiretroviral therapy and who had been therapy-naive so far was examined. To determine the possible presence of resistance, the virus RNA was first isolated from the plasma in the S3 laboratory. This was then transcribed into DNA, amplified, purified and sequenced. The sequences were analysed online by the "HIV DRUG RESISTANCE DATABASE" of Stanford University with regard to the subtype of the reverse transcriptase (RT), the protease and resistance to the common antiretroviral drugs with the following results: 1. The prevalence for primary resistance to antiretroviral drugs was 21.5 %. 2. Triple therapy drugs were affected with a prevalence of 10.53% in the group studied. 3. These results are worrying and confirm the thesis put forward by Kasang, Kalluvya et al. However, for the vast majority of patients studied, triple therapy would have been sufficient without costly and time-consuming resistance testing. The primary goal therefore remains to continue to use the financial resources for accessibility of drug treatment, as this is the best method to contain the spread of this pandemic. Nevertheless, further studies with even larger numbers of patients will be necessary in the coming years in order to constantly monitor the effectiveness of the current treatment regime and make adjustments if necessary.

The purpose of this mixed methods research study was to examine the role of adherence barriers to healthcare and the impact that such barriers have on highly active antiretroviral therapy (HAART) compliance for African Americans living with HIV/AIDS. HAART helps reduce HIV/AIDS morbidity and mortality. Of the 49% of study participants who had been out of medical care for more than 12 months, financial concerns were listed as the most common barrier (22.8%). Not having the support from family and friends (17.5%), being tired of going to doctor appointments (15.8%), health challenges (12.3%), lack of transportation (12.3%), and incarceration (12.3%) were also barriers in medical care that had a direct influence on noncompliance. The overall model of the linear regression analysis was significant, R2 = .469, adjusted R2 = .458, F(1, 49) = 43.24, p < .001. Being in medical care on a regular basis accounted for 46.9% of the total variance in attending primary care visits. The outcome of this analysis confirms the hypotheses (HA1) that attending 2 primary care visits within 6 months of being linked to care increased the rate of compliance for African Americans on HAART living with HIV/AIDS. The overall model of the linear regression analysis was significant, R2 = .469, adjusted R2 = .458, F(1, 49) = 7.206, p < .001. Being in medical care on a regular basis accounted for 46.9% of the total variance in attending primary care visits. The outcome of this analysis empasizes the importance of HAART compliance. These findings can lead to positive social changes by improving quality of life and health, which impacts gainful employment, sustains positive relationships, improves finances, and increases self-sufficiency

Introduction: Since its introduction, Highly Active Antiretroviral Treatment (HAART) has been shown to prolong the life expectancy of HIV-infected patients. HIV and HAART, especially protease inhibitors (PIs), have been associated with the occurrence of Metabolic Syndrome (MS). The objective of this systematic review and meta-analysis was to determine whether there is an association between the use of PIs and the incidence of MS in HIV-infected patients. Methods: A comprehensive search (including databases such as MEDLINE/PubMed, CENTRAL, LILACS and EMBASE) was performed. Observational studies published until November 2015 were included. Inclusion criteria for primary studies were: study population comprised HIV-infected patients aged 18 years or older and who were receiving HAART; patients assessed according to their use of PIs; DM as defined by the primary study. Heterogeneity was assessed and a pooled analysis was performed using a random-effects model. Results: 3 articles met the inclusion criteria, describing 586 HIV patients. Use of PIs was associated with the development of MS (RR: 2.11; 95% CI 1.28 to 3.48; 〖Chi〗^2:0.04, I^2: 0%; p-value 0.003). Conclusion: Use of PIs in HIV-infected patients is associated with an increased risk of MS. These findings are of relevance for future public policy because it will increase the interest in screening and prevention of MS in an expanding population. / Tesis

Bakgrund Humant immunbristvirus, HIV, är ett retrovirus, vilket innebär att viruset lagras i kroppens arvsmassa som leder till att personen med HIV aldrig blir av med viruset. HIV påverkar immunsystemet genom att förstöra eller skada celler nödvändiga för immunförsvaret. Då immunförsvaret har blivit så förstört att kroppen inte kan bekämpa andra sjukdomar eller tumörsjukdomar har HIV utvecklats till Acquired Immunodeficiency Syndrome, AIDS. På grund av inträdandet av antiretrovirala läkemedel år 1996 har HIV gått från att vara en sjukdom som förkortade livet till en kronisk sjukdom. Detta har medfört nya utmaningar för personer med HIV. Sjukdomen har en mångfacetterad påverkan på individen. Sjukdomen går framför allt ut över den upplevda hälsorelaterade livskvaliteten. Social, psykisk och fysisk hälsa är centrala delar för hur en individ hanterar att leva med kronisk sjukdom. Känsla av Sammanhang, KASAM, är en viktig beståndsdel för att hantera stressorer, som HIV, i livet. Ett lägre KASAM är ofta förknippat med negativ påverkan på hälsa. Omvårdnad av personer med HIV har förändrats från omvårdnad av sjukdom med ett snabbt förlopp till omvårdnad av kronisk sjukdom. Syfte Syftet var att undersöka hur vuxna personer med HIV upplever sin hälsorelaterade livskvalitet och hur de hanterar att leva med HIV som kronisk sjukdom med avseende på fysisk, psykisk och social hälsa. Metod Metod som valdes var en litteraturbaserad studie. För att hitta kunskaps brister i ämnet samlades, granskades, sorterades och sammanställdes den aktuella forskingen. Krav som ställdes på artiklarna är att de var av hög kvalité, etiskt granskade och innehöll en tydlig och klar frågeställning. Artikelsökningar gjordes via PubMed och Cinahl med relevansta Medical Subject Headings, Mesh-termer. Health-related quality of life fanns inte som MeSH-term men användes ändå i sökningar. Även manuella sökningar gjordes. 16 artiklar granskades i resultatet. Urvalskriterier för artiklarna var; publicerade efter år 2000, skrivna på svenska eller engelska samt att urvalsgruppen i studierna var vuxna. De inkluderade artiklarna presenterades i en matris där de klassificerades och värderades. Resultat I resultatet har det framkommit att KASAM, socialt stöd, graden av fysiska biverkningar av Highly Active Antiretroviral Therapy, HAART, sjukdomssymtom samt närvaro av depression påverkade hälsorelaterad livskvalitet hos personer med HIV. Strategier som användes för att hantera situationen var rationalisering, finna mening med livet, socialt stöd, terapi, styrning av negativa tankar, dela med sig av sin diagnos och hjälpa andra. Slutsats Socialt stöd, utbildning, information och etablerade copingstrategier kan påverka hälsorelaterad livskvalitet positivt och minska stigmat för personer med HIV. Omvårdnad för personer med HIV bör förbättras och utvecklas, med hjälp av utökad kunskap om sjukdomens påverkan på hälsans alla dimensioner.

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