A não adesão ao tratamento anti-retroviral implica no risco de falha terapêutica e queda da qualidade de vida. Objetivos. Estimar os níveis da adesão aos medicamentos anti-retrovirais (ARVs) na prática clínica e analisar fatores associados. Avaliar a concordância entre adesão auto-referida e as concentrações plasmáticas dos medicamentos ARV, numa sub-amostra. Métodos. Estudo de corte transversal, incluindo crianças e adolescentes não institucionalizadas, com idade entre um a 20 anos, atendidas no Instituto de Infectologia Emílio Ribas/São Paulo. Utilizou-se questionário estruturado e, para um sub-grupo, coletou-se sangue para dosagens plasmáticas de Efavirenz. Resultados. Dos 262 participantes do estudo, 40,1% não apresentaram adequada adesão aos ARVs, tomando até 89% das doses prescritas para o dia da entrevista e três anteriores. Os fatores que se mostraram associados à não adesão após o ajuste no modelo de regressão logística múltipla foram: ter dificuldades em usar ARVs por esquecer de tomar, residir com os avós, referir dificuldades em lidar com o tratamento ARV e como fator protetor, participar de atividades multiprofissionais. Foi demonstrada diferença significativa entre as médias das concentrações plasmáticas de Efavirenz para o grupo com e sem adesão adequada. Tendo como referência a mensuração da concentração plasmática do Efavirenz, o método da adesão auto-referida apresentou baixa sensibilidade e alta especificidade, sendo moderada a proporção de concordância entre os dois métodos (Kappa: 0,41). Conclusões. A dosagem das concentrações plasmáticas poderia ser incorporada na rotina de atendimento para acompanhamento da adesão ao Efevirenz. Considerando a baixa adesão aos medicamentos ARVs, torna-se importante estabelecer estratégias de acompanhamento envolvendo os fatores modificáveis associados à não adesão. / Non-adherence to anti-retroviral treatment results in therapeutic flaw risks and lower quality of life. Objectives: To evaluate the levels of adherence to anti-retroviral medicine (ARV) in clinical practice as well as to analyze associated factors. To evaluate conformity between self-reported adherence and plasmatic concentrations of ARV medicine in a subsample. Methods: A cross-sectional study, including non-institutionalized children and adolescents, ages from 1 to 20 years, who were assisted at the Infectology Institute Emílio Ribas / São Paulo. A structured questionnaire was used and, in one of the sub-groups, blood was collected for plasmatic dosages of Efavirenz. Results: Of the 262 study participants, 40,1% didn't not adhere to the ARVs, taking up to 89% of the prescribed doses for the interview day and for the three previous days. The factors which were linked to non-adherence after adjustment in the multiple logistics regression model were: difficulties in using ARVs due to forgetfulness, live with grandparents, difficulties with ARV treatment and as a protecting factor, participate in multiprofessional activities. As far as the Efavirenz there was a significant difference between the plasmatic concentrations of the groups with and without appropriate adherence. Using the plasmatic concentration of Efavirenz dosage as a reference, the self-reported adherence method had low sensibility and high specificity, and the conformity rates between the two methods were moderated (Kappa: 0, 41). Conclusion: The plasmatic concentrations dosages could be incorporate in the follow-up routine for adherence to Efevirenz. If we take in consideration the low adherence to ARVs, it will be important to establish follow-up strategies involving the modifiable factors associated to non-adherence.

A terapia gênica tem sido empregada em estudos pré-clínicos e clínicos, com o intuito de amenizar ou curar uma doença. Vetores retrovirais são uma ferramenta de transferência gênica largamente utilizada. Vetores bicistrônicos são uma alternativa interessante para o tratamento de doenças complexas. Na construção de um vetor bicistrônico pode-se empregar várias estratégias dentre elas a utilização da sequência IRES. A endostatina, fragmento do colágeno XVIII, tem sido muito utilizada na terapia anti-angiogênica devido sua ação inibitória no crescimento de células endoteliais. A imunoterapia tem sido utilizada como tratamento coadjuvante de tumores. Dentre as citocinas utilizadas, a interleucina-2 promovendo a proliferação de linfócitos T, tem sido utilizada em diversos estudos pré-clínicos e clínicos. O objetivo deste projeto foi construir e caracterizar in vitro um vetor retroviral bicistrônico codificando endostatina e interleucina-2 utlizando a sequência IRES. A construção do vetor foi realizada em três etapas, sendo comprovada a construção final por análise de restrição e seqüenciamento. Células de empacotamento foram transfectadas com o vetor, e posteriormente realizada a transdução na célula alvo. A endostatina e a interleucina-2 foram determinadas por Dot blot, seguido de análise da expressão por RT-PCR e ensaio de atividade. O vetor construído apresentou altos níveis de titulação viral, variando de 4.20x105 a 1.53x106UFC/mL. A determinação da endostatina e da interleucina-2 variaram entre 1.08 a 2.08g/106cels.24h e 0.66 a 0.89μg/106cels.24h, respectivamente. A expressão da endostatina no clone NIH3T3-pLend-IRES-IL2SN foi 2 vezes superior á apresentada pelo clone NIH3T3-pLend-IRES-IL2SN. A endostatina produzida promoveu uma inibição da proliferação de 40% das células endoteliais; e a interleucina-2 promoveu uma proliferação de 10.6% de linfócitos CD4 e 8.9% de CD8. Desta forma, a construção obtida neste trabalho representa uma excelente ferramenta para estudos da biologia celular do câncer e novas estratégias terapêuticas. / Gene therapy has been used in preclinical studies and clinical trials in order to alleviate or cure a disease. Retroviral vectors are a tool for gene transfer is widely used. Bicistronic vectors are an attractive alternative for treatment of complex diseases. A variety of options exists to simultaneously express two genes in genetically modified cells. The most common approach relies on bicistronic vectors in which the genes are linked to each other by an internal ribosome entry site allowing co-translational expression of both cistrons. Endostatin, the C-terminal fragment of collagen XVIII, is a potent angiogenesis inhibitor. At present, ES has been widely used in anti-angiogenic in a variety of experimental tumor models, and clinical trials to test it as an anti-tumor agent are already under way. Immunotherapy has been used as adjuvant treatment for tumors and has been used in several preclinical studies and clinical trials. The objective of this project was to construct and characterize in vitro an IRES-based bicistronic retroviral vector encoding endostatin and intereukin-2. The construction of the vector was performed in three stages, the final construction was analyzed by restriction analysis and sequencing. Packaging cells were prepared. The endostatin and interleukin-2 levels were determined by Dot blot. Monocistronic and bicistronic mRNA expression were analyzed by real time RT-PCR. Bicistronic vector showed high levels of virus trites, ranging from 4.20x105 to 1.53x106UFC/mL. Secreted levels of endostatin and interleukin-2 ranged from 1.08 to 2.08μg/106cells.24h and 0.66 - 0.89g/106cells.24h, respectively. The mRNA expression of ES in the NIH3T3 clone pLend-IRES-IL2SN was 2 times higher than the level presented by the NIH3T3 clone pLendSN. The endostatin promoted inhibition (40%) of endothelial cell proliferation. Interleukin-2 promoted a proliferation of 10.6% lymphocytes CD4 and 8.9% of CD8. We conclude that the IRES bicistronic vector provides a powerful tool for studies of cell biology of cancer and new therapeutic strategies.

A terapia gênica tem sido empregada em estudos pré-clínicos e clínicos, com o intuito de amenizar ou curar uma doença. Vetores retrovirais são uma ferramenta de transferência gênica largamente utilizada. Vetores bicistrônicos são uma alternativa interessante para o tratamento de doenças complexas. Na construção de um vetor bicistrônico pode-se empregar várias estratégias dentre elas a utilização da sequência IRES. A endostatina, fragmento do colágeno XVIII, tem sido muito utilizada na terapia anti-angiogênica devido sua ação inibitória no crescimento de células endoteliais. A imunoterapia tem sido utilizada como tratamento coadjuvante de tumores. Dentre as citocinas utilizadas, a interleucina-2 promovendo a proliferação de linfócitos T, tem sido utilizada em diversos estudos pré-clínicos e clínicos. O objetivo deste projeto foi construir e caracterizar in vitro um vetor retroviral bicistrônico codificando endostatina e interleucina-2 utlizando a sequência IRES. A construção do vetor foi realizada em três etapas, sendo comprovada a construção final por análise de restrição e seqüenciamento. Células de empacotamento foram transfectadas com o vetor, e posteriormente realizada a transdução na célula alvo. A endostatina e a interleucina-2 foram determinadas por Dot blot, seguido de análise da expressão por RT-PCR e ensaio de atividade. O vetor construído apresentou altos níveis de titulação viral, variando de 4.20x105 a 1.53x106UFC/mL. A determinação da endostatina e da interleucina-2 variaram entre 1.08 a 2.08g/106cels.24h e 0.66 a 0.89μg/106cels.24h, respectivamente. A expressão da endostatina no clone NIH3T3-pLend-IRES-IL2SN foi 2 vezes superior á apresentada pelo clone NIH3T3-pLend-IRES-IL2SN. A endostatina produzida promoveu uma inibição da proliferação de 40% das células endoteliais; e a interleucina-2 promoveu uma proliferação de 10.6% de linfócitos CD4 e 8.9% de CD8. Desta forma, a construção obtida neste trabalho representa uma excelente ferramenta para estudos da biologia celular do câncer e novas estratégias terapêuticas. / Gene therapy has been used in preclinical studies and clinical trials in order to alleviate or cure a disease. Retroviral vectors are a tool for gene transfer is widely used. Bicistronic vectors are an attractive alternative for treatment of complex diseases. A variety of options exists to simultaneously express two genes in genetically modified cells. The most common approach relies on bicistronic vectors in which the genes are linked to each other by an internal ribosome entry site allowing co-translational expression of both cistrons. Endostatin, the C-terminal fragment of collagen XVIII, is a potent angiogenesis inhibitor. At present, ES has been widely used in anti-angiogenic in a variety of experimental tumor models, and clinical trials to test it as an anti-tumor agent are already under way. Immunotherapy has been used as adjuvant treatment for tumors and has been used in several preclinical studies and clinical trials. The objective of this project was to construct and characterize in vitro an IRES-based bicistronic retroviral vector encoding endostatin and intereukin-2. The construction of the vector was performed in three stages, the final construction was analyzed by restriction analysis and sequencing. Packaging cells were prepared. The endostatin and interleukin-2 levels were determined by Dot blot. Monocistronic and bicistronic mRNA expression were analyzed by real time RT-PCR. Bicistronic vector showed high levels of virus trites, ranging from 4.20x105 to 1.53x106UFC/mL. Secreted levels of endostatin and interleukin-2 ranged from 1.08 to 2.08μg/106cells.24h and 0.66 - 0.89g/106cells.24h, respectively. The mRNA expression of ES in the NIH3T3 clone pLend-IRES-IL2SN was 2 times higher than the level presented by the NIH3T3 clone pLendSN. The endostatin promoted inhibition (40%) of endothelial cell proliferation. Interleukin-2 promoted a proliferation of 10.6% lymphocytes CD4 and 8.9% of CD8. We conclude that the IRES bicistronic vector provides a powerful tool for studies of cell biology of cancer and new therapeutic strategies.

<p>T lymphocytes can be rendered specific against a wide range of antigens by the genetic transfer of a chimeric receptor, a fusion between the antigen-binding domain of an antibody and the signalling domain of a T cell receptor. The use of such chimeric T lymphocytes has shown promising results for cancer therapy. Previous experiments in our laboratory have shown low rates of gene transfer using retroviral vectors. In this study, investigations have been done to increase the number of genetically modified cells. Different enhancers such as PLL and polybrene have previously been used in combination with retroviral transduction. The optimal retroviral protocol in this study showed to be the use of retrovectors produced with twice the normal concentration of the plasmids encoding env and gag-pol rather than the use of the enhancers. A 6-day pre stimulation of T lymphocytes prior transduction together with a centrifugation step increased the rate of modified cells even further. Alternative approaches of gene transfer were also investigated, including plasmid transfection and adenoviral transduction. While transfection protocols yielded low numbers of modified cells, adenoviral vectors showed the highest rate of gene transfer.</p> / <p>Cancer är den sjukdom som idag, efter hjärt-kärl-sjukdomar, kräver flest dödsfall i i-länder. Som en alternativ behandlingsmetod mot cancer pågår just nu forskning om genetiskt förbättrade immunceller, s.k. chimära T lymfocyter, skulle kunna användas för att döda tumörceller. De chimära cellerna är utrustade med en konstgjord receptor som är en fusion av en antikropp och en signalkedja. Det gör att cellerna kan riktas mot ett brett urval av cancertyper. Att få cellerna att ta upp generna som behövs för den konstgjorda receptorn har visats sig vara problematiskt. Den här studien har därför som mål att förbättra cellernas förmåga att ta upp gener. För detta har vi använt oss av retrovirus- och adenovirus-system tillsammans med försök att få cellerna att spontant ta upp generna, sk. plasmid-transfektion. Studien har visat att de båda virussystemen ger högst antal modifierade celler. Olika substanser som tidigare har visat sig förhöja graden av gentillförsel har testats, men vår studie har visat att tillverkningen av virusvektorerna har större påverkan på resultaten än någon av de olika hjälpmedlen.</p>

A não adesão ao tratamento anti-retroviral implica no risco de falha terapêutica e queda da qualidade de vida. Objetivos. Estimar os níveis da adesão aos medicamentos anti-retrovirais (ARVs) na prática clínica e analisar fatores associados. Avaliar a concordância entre adesão auto-referida e as concentrações plasmáticas dos medicamentos ARV, numa sub-amostra. Métodos. Estudo de corte transversal, incluindo crianças e adolescentes não institucionalizadas, com idade entre um a 20 anos, atendidas no Instituto de Infectologia Emílio Ribas/São Paulo. Utilizou-se questionário estruturado e, para um sub-grupo, coletou-se sangue para dosagens plasmáticas de Efavirenz. Resultados. Dos 262 participantes do estudo, 40,1% não apresentaram adequada adesão aos ARVs, tomando até 89% das doses prescritas para o dia da entrevista e três anteriores. Os fatores que se mostraram associados à não adesão após o ajuste no modelo de regressão logística múltipla foram: ter dificuldades em usar ARVs por esquecer de tomar, residir com os avós, referir dificuldades em lidar com o tratamento ARV e como fator protetor, participar de atividades multiprofissionais. Foi demonstrada diferença significativa entre as médias das concentrações plasmáticas de Efavirenz para o grupo com e sem adesão adequada. Tendo como referência a mensuração da concentração plasmática do Efavirenz, o método da adesão auto-referida apresentou baixa sensibilidade e alta especificidade, sendo moderada a proporção de concordância entre os dois métodos (Kappa: 0,41). Conclusões. A dosagem das concentrações plasmáticas poderia ser incorporada na rotina de atendimento para acompanhamento da adesão ao Efevirenz. Considerando a baixa adesão aos medicamentos ARVs, torna-se importante estabelecer estratégias de acompanhamento envolvendo os fatores modificáveis associados à não adesão. / Non-adherence to anti-retroviral treatment results in therapeutic flaw risks and lower quality of life. Objectives: To evaluate the levels of adherence to anti-retroviral medicine (ARV) in clinical practice as well as to analyze associated factors. To evaluate conformity between self-reported adherence and plasmatic concentrations of ARV medicine in a subsample. Methods: A cross-sectional study, including non-institutionalized children and adolescents, ages from 1 to 20 years, who were assisted at the Infectology Institute Emílio Ribas / São Paulo. A structured questionnaire was used and, in one of the sub-groups, blood was collected for plasmatic dosages of Efavirenz. Results: Of the 262 study participants, 40,1% didn't not adhere to the ARVs, taking up to 89% of the prescribed doses for the interview day and for the three previous days. The factors which were linked to non-adherence after adjustment in the multiple logistics regression model were: difficulties in using ARVs due to forgetfulness, live with grandparents, difficulties with ARV treatment and as a protecting factor, participate in multiprofessional activities. As far as the Efavirenz there was a significant difference between the plasmatic concentrations of the groups with and without appropriate adherence. Using the plasmatic concentration of Efavirenz dosage as a reference, the self-reported adherence method had low sensibility and high specificity, and the conformity rates between the two methods were moderated (Kappa: 0, 41). Conclusion: The plasmatic concentrations dosages could be incorporate in the follow-up routine for adherence to Efevirenz. If we take in consideration the low adherence to ARVs, it will be important to establish follow-up strategies involving the modifiable factors associated to non-adherence.

Magister Public Health - MPH / Background Nigeria accounted for 2.95 million of the 22 million people globally living with HIV in 2008. In 2010, the HIV prevalence increased to 3.1 million, with 1.5 million people requiring anti-retroviral treatment (ART). ART is effective if patients adhere to treatment (taking 95% or more of drugs as prescribed) over a sustained period. Taking less than 95% of the medication can lead to drug resistance and treatment failure, which have dire individual and public health consequences. This study described adherence to ART and the factors that constrain and motivate adherence among patients on ART at the University of Abuja Teaching Hospital in the Federal Capital Territory (FCT), Nigeria. Methodology An observational, descriptive and analytical, cross-sectional survey of adherence among 502 adult ART patients (254 women and 248 men) from the University of Abuja Teaching Hospital was conducted. I collected sociodemographic and clinical characteristics of participants, and barriers and facilitators to adherence. For the prescription refill data, I utilized the updated pharmacy refill records from the ART dispensary. Bivariate and multivariate analysis was performed to analyse the factors that influence adherence to ART. Results Participants in this study had been on therapy for a mean of 43±27 months. Total optimal self-reported adherence over the previous three days (not missing a dose, taking correct doses in the correct frequency and correct schedule) was 53.6%, compared with 62.5% adherence calculated by prescription refill. However, most (80.3%) participants achieved virologic suppression at a level of <400 copies/μl3. Reported barriers to adherence were: forgot (43%); travelled away from home (21%); ran out of medication (16%); busy at work (13%); lack of food (5%) and medication snatched by armed robbers (2%). Self-reported adherence over the previous three days was positively associated with age and viral load. Younger respondents (under 30 years) were 3 times more likely to adhere to their regimen compared with those older than 30 years (OR = 2.5; 95% CI = 1.26-4.61; p =

PhD (Sociology) / Department of Sociology / The purpose of the study was to investigate the influence of traditional healing practices on anti-retroviral treatment adherence in Vhembe District. This qualitative study used an explorative design to envisage the aim. A cross-sectional snowball sample was used to draw a sample of 9 participants from the 4 municipalities of Vhembe District. The data collection methods were; in-depth interviews, focus group discussions and key informants’ interviews. The 3 data collection techniques ensured triangulation for more complete and well-validated outcomes of the study. The researcher used the Van Manen method to analyse data. Contrary to popular belief that THPs promote non-adherence among people living with HIV/AIDS (PLWHA), the study found out that the majority of Traditional Healing Practitioners (THPs) encourage and positively influence PLWHA to adhere to anti-retroviral treatment. Apart from a minority of participants who claimed to cure HIV/AIDS, the majority acknowledged and admitted that traditional healing practices do not cure HIV/AIDS but it only heals opportunistic infections. As a result, the majority of THPs influences PLWHA to adhere to anti-retroviral therapy (ART). However, the positive influence of THPs is challenged by individual and social-cultural factors that are beyond THPs’ control which influence treatment adherence such as; traditional and cultural beliefs, side effects of ARVs, nurses’ attitude, inconveniences, lack of transport, personal choices, lack of trust in ARVs and fear of loss of the Disability Grant. It is on this backdrop that study findings prompted devising of a model and a 5 phase support program for intervention. / NRF

MPH, Maternal and Child Health, Faculty of Health Sciences, University of the Witwatersrand / Due to the high prevalence of HIV in South Africa, all pregnant women are offered an HIV test as part of the package of services offered during ante natal care (ANC). All women who present to an ANC clinic for the first time for that given pregnancy are given group talks about HIV and the availability of services to protect their children from HIV through Prevention of Mother to Child Transmission (PMTCT) services. Following these group discussions, all the women are then counselled on a one on one basis and are offered an HIV test. Women who decide not to take the test can opt out of testing at this stage, those who do go ahead and test are also offered post test counselling after which their test result is given to them. All HIV tests are conducted using rapid HIV test kits which make results known within 15 minutes, the results are given to the women on the same day of testing. Women whose CD4 count is below the antiretroviral treatment(ART) initiation threshold† are fast tracked onto ART , those whose CD4 is above the threshold should then be referred to other services which can help them maintain their health.1 These services are part of the Comprehensive Care, Management and Treatment (CCMT) approach. They include: CD4 count monitoring; treatment for opportunist infections; social workers, and support groups for psychosocial support.2 For purposes of this study, these services are collectively referred to as Wellness services. Thus PMTCT should serve as a gateway to either ART or Wellness services. This study therefore sought to describe the linkages between PMTCT, ART and Wellness by reviewing service utilisation levels and referral systems at sampled health facilities in Soweto. Data for this study were collected via a cross sectional record review of PMTCT registers and an ART initiation register at sampled health facilities. PMTCT registers were reviewed for the period January to March 2008 to determine what service had been given to pregnant women who accessed PMTCT services for the first time during that period † In his speech on World AIDS Day (December 1st 2009) President Jacob Zuma announced that CD4 count threshold for treatment initiation will be raised from 200 to 350 as of April 2010. 0707048E 2 and which follow on services they had been referred to. ART registers were reviewed for the period January to August 2008 to determine which of the pregnant women who had been referred to ART from the PMTCT service points at the sampled clinics accessed the service. Key informant interviews were also conducted with staff at PMTCT, ANC, ART and voluntary counselling and testing (VCT) service points at the sampled facilities. Descriptive statistics were run using SPSS version 17.0, comparisons were done using OpenEpi and key informant interview data were thematically analysed using Atlas TI version 5.2.0. Records at the PMTCT clinics showed that of the 1350 women who attended ANC clinics at the sampled facilities between January and March 2008, all but one agreed to test for HIV. Twenty-nice percent (388) tested positive for HIV. Of these 388 HIV positive women, 20% (77 women) had CD4 counts below 200 and were therefore eligible for initiation of ART. Review of records at the ART clinic showed that only 23% (n = 18, N = 77) of all ART eligible women had accessed the service. Review of the PMTCT register also showed that a significant proportion, 37% (n = 144, N =388), of women who tested HIV positive did not return to the clinics for their CD4 count results. These women therefore missed opportunities to access other follow on services to which they could have been referred and possibly ART as 31% (24 women) of these women were also eligible for ART. Review of records at Wellness services was not possible as no indications were made in the PMTCT registers of follow on services other than ART to which HIV positive women were referred. Thus the greater majority of women who were eligible for ART (77% of the 77 eligible women) did not access ART which they required to help them maintain their physical wellbeing. These women missed the opportunity to access holistic health care services, it is not known if they accessed ART services at other health facilities. Without the required antiretroviral therapy, it is highly likely that their women’s health status deteriorated such that they faced higher chances of morbidity and ultimately mortality. 0707048E 3 The review of records at both PMTCT and ART service points showed poor data management systems as referrals from PMTCT to ART were not always documented against client names in the PMTCT registers. Communication systems between the service points were also found to be poorly structured as there were no systematic feedback mechanisms on clients referred and seen. Linkages to Wellness services were even more poorly structured as no referrals to services which fall under Wellness were documented in the PMTCT registers. Key informants interviewed suggested several possible reasons why PMTCT and ART services were not being fully utilised as was evidenced by the of 37% of women who were not retained in care as they did not return for CD4 results and the low ART utilisation rate of 23%. Possible reasons suggestions were: ignorance of the need to access ANC services, preference for traditional medicine, fear of stigmatisation within their communities and poor staff attitudes towards patients. The key informants also suggested measures they thought could improve utilisation, these include hire of more staff, improved staff wages, improved interdepartmental communication and a bottom up approach to service improvement. A suggestion was also made to include PMTCT messaging in general HIV/AIDS information education communication material so as to raise awareness of the availability of PMTCT interventions. Although there were linkages between PMTCT, ART and Wellness services, these linkages were poorly developed and drop out from services was high. Efforts to follow up on patients or to retain them in care were not well developed as the data management systems employed by the service points were not consistently used nor did they facilitate patient monitoring and follow-up. Furthermore, the structural and managerial separation of the ART service point from PMTCT as well as the lack of standard protocols for referral to Wellness introduced barriers to service utilisation for women who required these services.

Master of 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.

Thesis (M.C.T.M. (Clinical Tropial Medicine))--Mahidol University, 2006. / LICL has E-Thesis 0012 ; please contact computer services. LIRV has E-Thesis 0012 ; please contact circulation services.