A Thesis submitted to the Faculty of Health Sciences (Internal Medicine), University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2017 / South Africa has the largest ARV treatment programme in the world, wherein highly active antiretroviral treatment (HAART) has improved the health related quality of life (HRQoL) in HIV/AIDS patients. On the contrary, cancers not previously associated with HIV/AIDS (non-Aids defining cancers; NADCs) have been shown to be increasing, compared to the AIDS defining cancers (ADCs). Lung cancer, as a NADC has been documented in the HIV/AIDS population as a leading malignancy. The poor understanding of the association between ARV drugs and lung cancer places a burden on public health, both globally and in South Africa (SA). Furthermore, the deregulation of the cell-cycle is one of the hallmarks of cancer, including lung cancer. The main aim of this study was to elucidate the effects of HAART components Efavirenz (EFV) and Lopinavir/ritonavir (LPV/r) on cell-cycle related genes in an in vitro lung cancer model. To achieve this, cellular based, molecular and Bio-Informatics approaches were employed. First, the cytotoxic effects of EFV (at 4, 13, 26, 50 μM) and LPV/r (at 10, 32, 50, 80 μM), for 24h, 48h and 72h on normal lung fibroblasts (MRC-5) and lung adenocarcinoma (A549) cells, were evaluated using the Alamar Blue (AB) assay. This was then followed by cell-impedance “xCELLigence” real-time cell analysis (RTCA) assay. This was done to determine the effects of EFV (at 4, 13, 50 μM) and LPV/r (at 10, 32, 80 μM) on cell viability, cell death and proliferation. Cell-cycle analysis using propidium iodide (PI) by Fluorescence-activated cell sorting (FACS) was done to quantify DNA present at each of the cell-cycle stages of the cell-cycle in response to ARV treatment. Subsequently, an apoptosis assay using Annexin V FITC and Propidium iodide (PI) dual staining by FACS was carried out to confirm and quantify the ARVs potential apoptotic effects. Then, 4′,6-diamidino-2-phenylindole (DAPI) staining was used to assess changes in nuclear morphology exerted by the ARVs’ effects. A more in depth interrogation of the cell-cycle was performed using a focussed gene array panel of some 84 human cell-cycle related genes. First, total RNA was isolated from both treated and untreated MRC-5 and A549 cells and reverse transcribed to cDNA for use as template in the PCR array reactions. From the array gene expression results, by convention a ±2 fold up-or-down-regulation was used as the basis of target selection. Following this, a real-time quantitative PCR (RT-qPCR) validation of selected genes of interest was done to quantify and confirm the PCR array results. This was followed by in-silico Bio-informatics analysis to map the molecular pathways regulated by the identified targets. For this purpose, STRING, Database for Annotation, Visualization and Integrated Discovery (DAVID), Reactome and Ingenuity Pathway Analysis (IPA) databases were used. Interestingly, double-edged oncogenic properties of both EFV and LPV/r at different concentrations were identified. The proliferative effects of EFV at 4, 13μM and LPV/r at10 μM, were elucidated, while 26, 50μM of EFV, and 32μM of LPV/r had slight inhibitory effects on cell proliferation. LPV/r at concentrations of 50 and 80μM exerted cytotoxic effects on the cells, as demonstrated by the AB and xCELLigence RTCA assays. Cell-cycle analysis using PI staining, particularly showed cell-cycle arrest at 32μM LPV/r, and a shift to G2/M by 13μM EFV, plasma relevant doses, compared to the untreated cells. An increasing apoptosis percentage was observed with increasing LPV/r concentrations, that is, 80μM LPV/r raised the apoptosis percentage almost two-fold compared to 32μM. This was coupled by necrosis, observed in a time-dependant manner. DAPI staining confirmed loss of nuclear integrity post ARV exposure, suggesting that both EFV and LPV/r impose damage to the genomic DNA. To further assess the observed changes in nuclear morphology, the effects of EFV and LPV/r on the expression of an arrayed panel of human cell-cycle genes in cancer and normal lung cells was determined. Significantly differentially expressed targets were identified and further quantified and confirmed by RT-qPCR. Such targets included ATM, p53, cyclin-dependant kinase inhibitors (CDKIs), such as, p21, aurora kinase B (AURKB), Mitotic Arrest Deficient-Like 2 (MAD2L2) and the apoptosis related gene, caspase 3 (CASP3). Bio-Informatics analyses revealed close and direct protein-protein interactions (PPIs) between these targets, notably, with change in interaction between the gene products involved in DNA repair mechanisms, observed between ARV treated and untreated groups, as illustrated by STRING interactions. DAVID, Reactome and IPA analysis showed changes in expression of genes related to stress and toxicity and DNA damage response genes. In particular, ATM, p53 and its downstream targets such as GADD45A (growth arrest and DNA damage inducible alpha) gene were up-regulated by ARV treatment, while cyclin/CDK activity was down-regulated, resulting in reduced cell proliferation. Thus in summary, both EFV and LPV/r altered the expression levels of cell-cycle related genes, influencing overall cellular health, acting to either inhibit or stimulate cell proliferation. This suggests EFV’s and LPV/r’s proliferative and inhibitory roles in the proliferation of lung cells. Moreover, future directions can include the transfection of lung cells with HIV provirus followed by treatment of the cells with the same ARVs under study. This could be substantiated by including HIV positive patient samples on and off ARV drug treatment with lung cancer, including HIV negative patients with cancer as one of the controls. / MT2018

MPH, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 2010 / INTRODUCTION Although much focus has been placed towards rapid scale-up of antiretroviral treatment programmes and interventions for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV), very little is known about adherence to highly active antiretroviral therapy (HAART) and loss to follow-up of pregnant women in antiretroviral treatment programmes in the developing world. In this retrospective cohort analysis, we described the baseline characteristics of adult women who were pregnant at the time of HAART initiation (pregnant at start) as well as women who became pregnant during follow-up after starting HAART (pregnant after) and women who never had a pregnancy (not pregnant) during the study period. We evaluated the association of pregnancy status with adherence and loss to follow-up in these three groups of women. MATERIALS AND METHODS Themba Lethu Clinic is an urban public-sector antiretroviral rollout facility in Johannesburg, South Africa. A retrospective analysis was conducted of all adult women initiating HAART at this clinic between January 2005 and December 2007. Clinical data from these patients was analysed for differences in rates of loss to follow-up, and measured adherence rates based on CD4 cell count response and virologic suppression. Regression models were performed to determine independent predictors of adherence and loss to follow-up and compared between the three groups. Survival analysis, in the form of Kaplan-Meier plots and log-rank tests, was used to compare the time to becoming lost to follow up. RESULTS Between 1 January 2005 and 31 December 2007, 5129 women initiated HAART at Themba Lethu Clinic, Johannesburg, South Africa. Of these women, 521 (10.0%) were pregnant at the time of HAART initiation (pregnant at start) and 291 (5.6%) became pregnant during follow-up (pregnant after). Women who were pregnant at start (16.6%) of HAART had less-advanced HIV disease than the not pregnant women and pregnant women after HAART initiation 4608 (89.9%). Overall pregnant women were significantly younger than the not pregnant women and fewer pregnant women had a CD4 <100 cells/mm3 and a WHO stage III of HIV disease. There was no significant difference in the CD4 cell count response and virological suppression between the three groups of women based on pregnancy status at 6 months and 12 months (X2=2.1, p=0.347 and X2=4.4, p=0.111 respectively). However, women pregnant at start were more likely to become lost to follow-up (X2=15.8, P=<.0001) during follow up. In the multivariate Cox logistic regression model, independent predictors of loss to follow-up were pregnancy, baseline CD4 cell count and age at initiation. Being pregnant was significantly associated with being loss to follow-up. CONCLUSIONS Pregnancy is significantly associated with defaulting treatment and becoming lost to follow-up from HAART treatment programmes. Together with being pregnant, young age and a low CD4 at baseline are high risk factors for non adherence and loss to follow-up in this sub-group of the population. Early initiation of HAART with adequate pre-treatment counselling and ongoing adherence support could help improve adherence and retention in care for patients in treatment programmes in resource-limited settings. Interventions to trace patients immediately upon missed appointments would help to reduce the number of patients’ loss to follow-up. Moreover, integration of tuberculosis (TB), antenatal care (ANC) and HIV treatment services may maximize the effectiveness of interventions aimed at reducing the loss to follow-up rate. The initiation of HAART in pregnancy requires strengthened antenatal and HIV services that target women with advanced stage disease.

This research investigated the ethical and legal issues that impact on the urgent implementation of Nurse Initiated and Managed Anti-Retroviral Treatment (NIMART) in South Africa, which is part of the task-shifting strategy recommended by the World Health Organization (WHO) to deal with the human resource shortage that has negatively impacted access to Anti-Retroviral Treatment (ART) in developing countries (WHO;2006). The objectives were to review and analyse the existing legal framework and provisions for NIMART in South Africa; and to identify ethical issues and implications of NIMART within the current legal framework. It analysed the legal issues that impact on the implementation of NIMART within the public health service in South Africa, as well as the ethical basis and implications of NIMART on the practice of nurses in the scale-up of Anti-Retroviral Treatment in Primary Health Care (PHC). A comparative analysis was done with case studies of task-shifting in other developing countries and evidence-based recommendations for an enabling and long-term sustainable ethico-legal approach to task-shifting were established. The research concluded that despite the existing legal framework for NIMART in South Africa being firmly founded in the Constitution and further enabled by health policy, challenges exist in implementation of certain critical aspects of the enabling legislation relating to nurse training and accreditation required for full authorization to practice NIMART and that these technical challenges if not attended to could threaten the long-term sustainability of NIMART.

MPH, Faculty of Health Sciences, University of the Witwatersrand / Background: The increase use of highly active antiretroviral therapy (HAART) among patients with HIV infection and AIDS has led to increasing reports of metabolic abnormalities such as diabetes mellitus, hypertension, dyslipidaemia and obesity. Therefore, it is important to explore the burden of these diseases among HIV infected patients. Objectives: To determine the burden of metabolic diseases (hypertension, diabetes, obesity and dyslipidaemia) in patients attending HIV clinic at the Charlotte Maxeke Johannesburg Academic Hospital (JHBH). Methodology: It was a cross-sectional study. The study population included patients attending JHBH HIV clinic and on HAART for more than one year. A sample size of 304 patients, including 237 females and 67 males partook in this study. Anthropometric measurements were taken from patients and blood samples of these patients were sent to laboratory for lipograms, HbA1c, random glucose, CD4 lymphocytes counts as well as HIV viral load testing. The data was analysed with standard statistical software Epi-info version 6.0. Both descriptive and analytical statistics was used. Results: The prevalence of metabolic syndrome according to the IDF was 20.4 %; obesity (BMI 30 kg/m2) was 16.8% and patients that were overweight (BMI > 25 kg/m2 and BMI < 29.9 kg/m2) was 28.6%; hypercholesterolemia (TC 5.0 mmol/l) = 35.5%; HDL< 1.29 mmol\L in females was 58% and HDL <1.04 mmol/l in males was 36%; elevated triglycerides 1.7 mmol/l was 30% and only 16% was classified as being hypertensive (BP 140/90 mmHg and / or on Hypertensive medication). The majority of the patients (86.2%) had a CD4 lymphocyte count 200 X 106 cells/l and 84% of patients had less than detectable limits for viral loads (VL< 40 copies / μl), which has been reported as optimum levels for metabolic diseases in HAART recipients. Conclusion: These results clearly indicate that there is a growing burden of metabolic diseases among HIV patients on HAART attending the Johannesburg hospital HIV clinic. The current study also indicates that the metabolic disturbances are more frequent in women than in men, except for hypertension.

The study explores pertinent issues around a comprehensive provision of antiretroviral drugs to HIV positive pregnant women in South Africa from a human rights perspective. Although these drugs have been proven to significantly reduce the transmission of HIV from a pregnant mother to her newborn baby/babies at birth, the South African government for over five years refused to roll them out in the public health sector. Reasons that were provided in this regard were multifaceted and have included claims regarding their alleged toxicity, potential side effects, huge cost, inadequate infrastructure, etc until March 2004 when it announced to start a national rollout program. It is in light of this that the study sets out to explore some of the key positions within the government and amongst activist groups on the health rights of HIV positive pregnant women, and how these different positions have evolved in response to each other. In particular, the paper aims at examining how discourses of human rights were employed, and how they have impacted on the Social Work discipline. It further focuses on developing a Social Work perspective on the human rights of HIV positive pregnant women in South Africa, thereby contributing to the discipline’s professional value base and body of knowledge, which inform, inter alia, its advocacy role and social action approach. The research project was embedded in a theoretical framework often referred to as ‘standpoint research’. An archival study of local and international literature and policy documents was conducted. This was complemented with a limited qualitative study. Semi-structured interviews were conducted with a purposive sample of five interviewees representing a cross-section of positions on the topic. This data was analyzed using a three step coding procedure that allowed for categorizing, connecting, and systematically relating the gathered data to each other and to the reviewed literature. The research findings indicate that the South African government’s absence of consistency and apparent lack of political will to rollout the drugs have contributed to the deterioration of the right of HIV positive pregnant women to access health care services. The role of civil society organizations in helping to realize, promote and protect the health and related human rights of this group is emphasized. It was also found that the different strategies employed to this end speak well to Social Work’s value base, and some of its methods and approaches to practice. Social Work is therefore well placed to join and support those efforts of other segments of civil society that have been investigated in this paper. The paper concludes by making recommendations towards, inter alia, the need for the South African government to adhere to the values enshrined in the country’s Constitution; to work closely and transparently with different organs of civil society; and simultaneously implement the said ARV rollout program while building and strengthening its infrastructural capacity. The various roles Social Work could, and should, assume with regards to improving the human rights of HIV positive pregnant women in this regard are also highlighted.

As novas drogas para tratamento do HIV/aids mudaram a história da doença, diminuindo a morbimortalidade e possibilitando um tratamento seguro e tolerável ao portador. Entretanto, para se alcançar os benefícios do tratamento é necessário o uso correto e diário dos medicamentos gerando um novo desafio: a adesão a TARV. A interação do paciente com a equipe multiprofissional tem sido associada ao aumento crescente da adesão. A inserção do farmacêutico nesta equipe é relativamente recente e tem potencial de impactar positivamente na adesão. Neste contexto, este trabalho teve como objetivo avaliar o impacto de intervenções farmacêuticas na adesão ao tratamento antirretroviral em pacientes com HIV/aids. Para alcançar os nossos objetivos foi realizado um estudo de intervenção (pesquisa-ação), prospectivo com análise quali e quantitativa. Foram convidados a participar do estudo os pacientes que já estavam em uso de TARV há pelo menos 12 meses antes do inicio do estudo e que apresentavam história de má adesão (grupo 1) e pacientes que iriam começar a TARV no momento de sua inclusão no estudo (grupo 2). A adesão foi avaliada por meio de questionários estruturados, pelos exames laboratoriais de contagem da carga viral e contagem do linfócito TCD4, e do histórico de retiradas dos medicamentos. O acompanhamento farmacêutico aconteceu por um período de 12 meses onde foram enviadas mensagens de texto SMS (torpedos) para os pacientes com objetivos de lembra-los da consulta com o farmacêutico e da retirada da TARV. Foram convidados a participar do estudo 120 pacientes, sendo que 95 concluíram o acompanhamento farmacêutico. Deste total, 63 pacientes pertenciam ao grupo 1 e 32 pertenciam ao grupo 2. Após 12 meses de seguimento farmacêutico, entre os 63 pacientes que já estavam em tratamento, houve aumento do percentual de boa adesão de 16% para 57%, com aumento do CD4+, e aumento do percentual de pessoas (de 21% para 52%) com carga viral indetectável. Para o grupo que iniciava a TARV pela primeira vez, 69% teve boa adesão e 91% teve queda significativa da carga viral após 12 meses de acompanhamento. Diante destes resultados, é possível concluir que ha uma tendência no aumento da adesão quando a equipe multiprofissional conta com um farmacêutico que atua de forma clínica junto ao paciente. / Antiretroviral therapy (ART) has changed the history of HIV/aids, reducing morbi-mortality and providing a safe and tolerable treatment. However, to achieve all the benefits from the treatment its expected a correct and daily use of medicines, which means the challenge of adherence to ART. Its known that an effective interaction between patient and the multidisciplinary team is linked to good treatment adherence. The insertion of a clinical pharmacist in this team is recent and it has the potential to positively impact in adherence and HIV control. This study aimed to assess pharmaceutical interventions on adherence to ART in HIV/aids patients. We designed an interventional and prospective study, including qualitative and quantitative analysis. Patients with poor history of adherence to ART, detected by the multiprofessional team (Group 1) were included. These patients should have been using ART at least 12 months before their entrance in the study. In the other group we invited people with recent HIV diagnosis and with ART prescription for the first time (Group 2). Adherence was assessed through structured questionnaires, laboratory exams of viral load count and CD4+ lymphocyte count, and by withdrawal of medicines. The pharmaceutical monitoring had been done during 12 months, in which text messages (SMS messages) were sent for patients to remind them about the pharmacist and medical appointments as well as the withdrawal of ART. An amount of 120 patients were invited to participate in the study, and 95 completed the pharmaceutical monitoring. Of this total, 63 patients belonged to Group 1 and 32 belonged to Group 2. After 12 months of pharmaceutical monitoring, among group 1 (63 patients) there was an increase in the percentage of adherence from 16% to 57%, an increase of CD4+ (median of 199 to 301cel/mm3) and an important raise in the percentage of people with undetectable viral load (from 21% to 52%). For Group 2 that started ART for the first time, 69% had a good adherence and 91% had a significant drop in viral load, after 12 months of follow-up. Based on these results, we can conclude that adherence and HIV control increases significantly when the multidisciplinary team has a pharmacist who works close to the patient and the healthcare team.

Orientador: Lenice do Rosário de Souza / Banca: Jussara Marcondes Machado / Banca: Marli Teresinha Gimenis Galvão / Banca: Gimol Benzaquen Perosa / Banca: Nelson Silva Filho / Resumo: O "HIV/aids - Quality of life" (HAT-Qol) é um instrumento específico multidimensional utilizado para mensurar a Qualidade de Vida de indivíduos infectados pelo HIV. É dividido em nove domínios, a saber, atividade geral, atividade sexual, preocupação com sigilo sobre a infecção, preocupação com a saúde, preocupação financeira, conscientização sobre o HIV, satisfação com a vida, questões relativas à medicação e confiança no médico. O presente estudo analisou a qualidade de vida de indivíduos com infecção pelo HIV ou aids atendidos no Programa de DST/Aids no município de Maringá (PR), relacionando com o uso ou não de terapia anti-retroviral (TARV) e as características sócio-demográficas, epidemiológicas e clínicas. A coleta de dados foi realizada, pela análise retrospectiva dos prontuários dos 1.200 pacientes cadastrados no Serviço e, a seguir, foi aplicado o instrumento HAT-Qol, no momento anterior à consulta médica ambulatorial de rotina. Preencheram os critérios de inclusão 169 pacientes com diagnóstico confirmado de infecção pelo HIV, que foram divididos em dois grupos de estudo, G1 com 118 indivíduos em uso de TARV e G2 com 51 sem uso de TARV. Na análise dos resultados, quanto às características sócio-demográficas, observou-se que, não houve influência nas respostas, em nenhum Domínio, em relação a gênero, grau de escolaridade e opção sexual. Houve influência da faixa etária em relação ao Domínio que avalia a satisfação com a atividade sexual e do estado civil em relação ao Domínio que avalia a conscientização sobre o HIV, nos quais obtiveram menor índice nas respostas ou pior qualidade de vida, respectivamente, os homens de 50 a 69 anos e os pacientes sem parceiros fixos em relação aos casados ou amasiados. Observou-se, ainda, que o tempo de diagnóstico da doença exerceu... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The "HIV/aids - Quality of life" (HAT-Qol) is a specific multifunctional instrument used to measure the Quality of life of HIV infected people. It's divided in nine domains that are, general activity, sexual activity, concern about the infection secrecy, concern about health, financial concern, awareness about HIV, satisfaction with life, issues about medications and belief in the doctor. The current study has analyzed the quality of life of HIV or aids infected individuals attended in the DST/Aids Program in Maringá city, Paraná state, in relation with the use or not of antiretroviral therapy (TARV) and the social-demographic, epidemiological and clinical characteristics. The data collect was performed, by the retrospective analysis of the 1200 prontuaries of patients registered in the Service and, then, the HAT-Qol instrument was applied right before the routine ambulatory medical consultation. 169 patients had fit the inclusion criteria of HIV infection diagnosis confirmed, which were divided in two groups of study, G1 with 118 individuals in use of TARV and G2 with 51 individuals not using TARV. In the analysis of the results, in respect of the social-demographic characteristics, it was observed that it didn't influence the answers in any Domain, in respect of the gender, educational degree and sexual option. The age rate influenced the Domain which evaluates the satisfaction with the sexual activity and of the marital status in relation with the Domain that evaluates the awareness about HIV, in which they had the lowest response index or the worst quality of life, respectively, the men between 50 and 69 years-old and the patients who didn't have regular partners compared with the ones who were married or concubine. It was observed yet that the time of the disease's diagnosis influenced the Domains... (Complete abstract click electronic access below) / Doutor

"Host resolution of viral infection is dependent upon components of the innate and acquired immune system. The mammalian protein Apobec3 plays an important role as part of the immune system’s innate defenses through its modification of reverse transcribed viral DNA. Recently, Apobec3 was found to directly inhibit HIV-1 and HBV replication through deaminating newly transcribed deoxycytidine residues to deoxyuridine. The ability of mouse and simian Apobec3 variants to inhibit human retroviruses and vice versa highlights the utility of analyzing cross-species homologues. To better understand this editing enzyme, differentially pathogen-susceptible inbred mice were used as an experimental model. The purpose of this project is to examine the effects of murine Apobec3 (muA3) alternative splicing on its DNA-editing characteristics. Three distinct Apobec3 isoforms were isolated from pathogen-susceptible BALB/cByJ (“C”) inbred mice, and two Apobec3 isoforms came from pathogen-resistant C57BL/6ByJ (“Y”) mice. The five muA3 isoforms were cloned, sequenced, and expressed from a constitutive promoter in a haploid Saccharomyces cerevisia strain. MuA3 DNA-editing activity was measured via the CAN1 forward mutation assay. The five isoforms studied in this project were discovered to be strain-specific. One isoform from each mouse strain mutated the yeast CAN1 locus significantly. Additionally, both muA3 isoform mRNAs derived from the pathogen-resistant Y mice were found to persist at a higher level (2.7 -12.4 fold) than any of the C mouse isoforms. This suggests that the absence of exon 5 or some other signal in the Y mice may influence transcript stability. Evidence also suggests that the murine Apobec3 start codon is actually 33bp upstream of its reference start, with implications for previous research performed using muA3. Sequencing analysis of genomic DNA revealed the presence of a 4bp insertion in a region of BALB/cByJ muA3 which may have disrupted an intronic splicing enhancer signal. Furthermore, a novel BALB/cByJ Apobec3 isoform was characterized. This is the first report of strain-specific processing with regard to muA3."

As access and use of antiretroviral therapy continue to increase, the need to improve antiretroviral toxicity monitoring becomes more critical. This is particularly so in underserved settings, where patterns of antiretroviral toxicities possibly alter the need for and frequency of antiretroviral toxicity monitoring. However, barriers such as few skilled healthcare providers and poor infrastructure make antiretroviral toxicity monitoring in underserved settings difficult. The purpose of this dissertation was to investigate how standard clinical guidelines, knowledge-based clinical decision support, and task delegation could be leveraged to overcome barriers to antiretroviral toxicity monitoring in underserved settings. The strategy adopted in this dissertation was guided by the Design Science Research Methodology that emphasizes the generation of scientific knowledge through building novel artifacts. Two qualitative descriptive studies were conducted to characterize the contextual factors associated with antiretroviral toxicity monitoring in underserved settings. Supported by the findings from these studies, a knowledge-based software application prototype that implements clinical practice guidelines for antiretroviral toxicity monitoring was developed. Next, a quantitative validation study was used to evaluate the structure and behavior of the prototype’s knowledge base. Lastly, a quantitative usability study was conducted to assess lay health worker perceptions of the satisfaction and mental effort associated with the use of checklists generated by the prototype. This dissertation research produced empirical evidence about the broad motives and strategies for promoting medication adherence, safety, and effectiveness in underserved settings. It also identified barriers and facilitators of antiretroviral toxicity monitoring within ambulatory HIV care workflows in underserved settings. Additionally, it provided evidence about the extent to which antiretroviral toxicity domain knowledge could be implemented in a knowledge-based application for supporting point-of-care antiretroviral toxicity monitoring. Lastly, the research provided previously unavailable empirical evidence about the perceptions of lay peer health workers on the use of checklists for the documentation of antiretroviral toxicities.

Magister Public Health - MPH / Background: The Zambian anti-retroviral therapy (ART) program has successfully enrolled over 770, 000 people living with HIV (PLWH), out of a population of 1.2 million PLWH. This tremendous success has overburdened the clinic system resulting in many challenges for both patients and healthcare staff. To promote ART initiation, adherence, and retention and at the same time relieve pressure on the health system, a home-based ART delivery model (HBM) was piloted in two urban communities of Lusaka. This study explored levels of acceptability of the model and factors influencing this among PLWH living in the two communities. Acceptability was defined as degree of fit between the patient’s expectations and circumstances and the home-based delivery model of ART, taking into consideration all the contextual elements surrounding the patient. Methodology: A qualitative study of HBM acceptability was nested within a clusterrandomized trial comparing outcomes in patients receiving HBM intervention compared to the standard of care in two communities in Lusaka, Zambia. Using an exploratory qualitative study design and a purposive sampling technique, qualitative data were collected using observations of HBM delivery (n=12), in-depth interviews with PLWH (n=15) and Focus Group Discussions with a cadre of community health workers called community HIV care providers (CHiPs) administering the HBM (n=2). Data were managed and coded using Atlas.ti 7 and analysed thematically. Results: Overall, the HBM was found to be a good fit with the lives and expectations of PLWH and therefore highly acceptable to them. This acceptability was influenced by a combination of cross cutting clinic based, program design and socio-economic factors that have been categorized into push and pull factors. Push factors were those related to the challenges that PLWH faced when accessing ART from the clinic and included congestion, long waiting times, confidentiality breaches and stigma arising from attending a dedicated clinic. These factors resulted in considerable direct and indirect livelihood opportunity costs. The HBM as an alternative had a number of ‘pull factors’. PLHW described services offered through the model as convenient, confidential, trusted, personalized, less stigmatizing, comprehensive, client centred, responsive, and respectful. Disclosure of client’s HIV status to people they lived with was found to be critical for the acceptability of the model. Conclusions and recommendations: The HBM is highly acceptable and this acceptability is influenced by a combination of crosscutting push and pull factors. Key to the HBM’s acceptability was its delivery design that was responsive to individual patient needs and the steps CHiPs took to minimize the ever-present threat of disclosure and stigma. Future adoption and scaling up of HBM should recognize the importance of these design features.