This study sought to explore and describe the perceptions and beliefs of physicians about adherence to antiretroviral treatment by patients in the South-East district of Botswana. The Health Belief Model (Naidoo & Willis 2003:222) was adapted to suit and be used in the study. A descriptive, exploratory qualitative design was used. Unstructured interviews and unstructured observation data collection methods were applied. Informed consent was obtained prior to data collection. For triangulation purposes, observations were done following interviews, and data analysis was done by two different people. The findings of the study revealed that the perceptions and beliefs of treating physicians contributed towards adherence. Physicians perceived adherence as an important aspect in the success of antiretroviral treatment. Giving patients correct information, personal motivation, patients' understanding of treatment, traditional and religious beliefs were among other factors perceived by physicians to be impacting on adherence. / Health Studies / M.A. (Public Health)

The aim of the study was to determine the factors that influence adherence to ART among adolescents who contracted HIV through vertical transmission. Qualitative research using descriptive phenomenology was conducted at Botswana-Baylor Children’s Clinical Centre of Excellence. Data was collected using in-depth individual semi-structured interviews. Eight (8) adolescents between 14 and 19 years who had been on ART for minimum of 4 years were interviewed. Thematic analysis of data was done and five (5) themes emerged from the participants' description of the experience of taking ART over a long period of time. The themes that emerged indicated the factors that influence adherence to ART, and they included knowledge and positive beliefs about ART, need for support, ART difficult treatment regimen, having a regular doctor and psychosocial emotional needs. The findings suggested that the adolescents who contracted HIV through vertical transmission require support while continuing on a simplified long-term ART regimen after an assessment of their psychological well beings and periodic checks. / Health Studies / M.A. (Public Health)

Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) is a global problem. Introduction of antiretroviral therapy (ART) came as a relief to people living with HIV and AIDS as it improved their quality of life. However, maintaining high adherence levels to antiretroviral treatment is still a challenge in some settings yet strict adherence to treatment instructions is critical for successful suppression of HIV. A qualitative, descriptive phenomenological research was conducted to explore factors that influence adherence to antiretroviral therapy at Beatrice Road Infectious Disease Hospital (BRIDH). Purposive homogenous sampling was done. Data was collected from twenty patients through in-depth interviews. Study findings identified five main themes that facilitate adherence and these entail knowledge on HIV and AIDS and ART, motivation to live, adherence support networks, good service delivery and factors related to medication / Health Studies / M.A. (Public Health)

The purpose of the study was to evaluate the IMB skills model for its relevance to the Ethiopian context. According to the model, adherence-related information and motivation work through adherence-related behavioural skills to affect adherence to ART. Quantitative, analytical, observational, cross-sectional, institution-based study was conducted to evaluate the model by assessing those patients who have and do not have the right information, motivation, and behavioural skills whether they have or do not have good adherence to ART. Data was collected using structured questionnaires where a total of 400 randomly selected participants provided data on adherence-related information, motivation and behavioral skills as well as adherence behavior per se. Data was analysed using the Statistical Package for Social Sciences (SPSS) version 20.0. Both descriptive and inferential statistics used in the study. Only 90.75 % of the total sample population reported ART adherence rate of more than or equal to 95% in this study. Free and restricted model tests, through bivariate and multivariate analyses, used to assess the propositions of the IMB model of ART adherence and provided support for the interrelations between the elements proposed by the model. The study has supported the applicability of the IMB model of adherence to the Ethiopian context highlighting its application in adherence-promotion intervention efforts. The findings revealed the need for on-going educational, informational and other interventions to address the knowledge, motivation and adherence behavioural skills of patients in order to improve the current levels of ART adherence behaviour. / Health Studies / D. Litt. et Phil. (Health Studies)

INTRODUÇÃO: Pacientes em terapia anti-retroviral podem apresentar escapes transitórios de viremia plasmática (blip), porém os preditores desse evento e seu impacto sobre a incidência de falência virológica são ainda controversos na literatura. Neste estudo de coorte estimou-se a incidência de blip e de falência virológica e investigaram-se possíveis preditores de tais desfechos. Blip foi definido como carga viral superior a 50 cópias/mL com subseqüente supressão da viremia plasmática e falência virológica como duas medidas consecutivas de carga viral plasmática superiores a 50 cópias/mL. Adicionalmente, pesquisou-se, por ocasião desses eventos, a presença de mutações genotípicas de HIV capazes de conferir resistência aos anti-retrovirais e as concentrações plasmáticas de inibidores não nucleosídicos da transcriptase reversa e inibidores da protease, comparando-as com o relato dos participantes sobre adesão à medicação. MÉTODOS: 350 participantes infectados pelo HIV (250 homens e 100 mulheres) foram selecionados no Serviço de Extensão ao Atendimento de Pacientes com HIV/Aids Casa da Aids do Hospital das Clínicas da FMUSP, São Paulo, Brasil. Na admissão ao estudo e trimestralmente, ao longo de 78 semanas, foram coletadas informações sobre dados sóciodemográficos, forma presumida de aquisição do vírus, uso de e adesão a medicações anti-retrovirais, ocorrência de outras comorbidades, bem como uso de álcool e de drogas ilícitas. Investigaram-se fatores potencialmente associados à incidência dos desfechos de interesse, tais como ocorrência de outras doenças, exposição a imunizações e falha na adesão a práticas de sexo mais seguro. Amostras de sangue periférico foram coletadas a cada visita para determinação de carga viral plasmática por RT-PCR ultrassensível, e contagem de linfócitos T CD4+ por citometria de fluxo. Nos indivíduos que apresentaram os desfechos de interesse do estudo, procedeu-se ao seqüenciamento dos genes da transcriptase reversa e da protease de HIV e à dosagem plasmática dos anti-retrovirais por método de Cromatografia Líquida de Alta Performance. As incidências de blip e falência virológica foram estimadas e os fatores associados a ambos investigados em modelo de regressão logística múltipla. RESULTADOS: As incidências de blip e falência virológica foram 9,4 e 4,2/100 pessoas-ano, respectivamente. Três indivíduos apresentaram falência virológica precedidos por blip. À análise multivariada, a não adesão às praticas de sexo mais seguro no mês precedente se mostrou independentemente associada à ocorrência de blip (OR 24,64, IC 95% 4,40 137,88, p<0,001) e de falência virológica (OR 24,69, IC 95% 4,20 145,18, p<0,001). Adicionalmente, observou-se que a exposição prévia a maior número de esquemas anti-retrovirais foi preditora dos eventos blip (OR 1,82, IC 95% 1,41 2,36, p<0,001) e falência virológica (OR 1,67, IC 95% 1,19 2,35, p=0,003). A ocorrência de blip não se associou ao desenvolvimento posterior de falência virológica. Um maior número de mutações conferidoras de resistência medicamentosa foi identificado no momento de falência virológica, quando comparado ao momento de blip, com predomínio de mutações no gene da transcriptase reversa, refletindo o maior uso desses fármacos. Das 122 concentrações plasmáticas de anti-retrovirais analisadas em 120 amostras, 84 estavam em níveis terapêuticos adequados. Porém, tais resultados apresentaram apenas 69% de concordância com a adesão auto-referida à medicação. Este estudo mostra que apresentar blip em uma medida isolada pode ser um evento benigno; por outro lado, falência virológica pode ser conseqüente a acúmulo de mutações conferidoras de resistência a pelo menos um dos anti-retrovirais em uso, podendo comprometer a eficácia do esquema terapêutico utilizado. Ambos os desfechos mostraram-se mais incidentes na população multiexperimentada à terapêutica, que, portanto, merece atenção particular. Uma importante contribuição deste estudo foi a avaliação da dosagem plasmática dos antiretrovirais, método simples e de baixo custo, que, implantado na rotina laboratorial, pode contribuir para o monitoramento da adesão aos antiretrovirais e reduzir a demanda por testes genotípicos / BACKGROUND: HIV-1-infected patients under antiretroviral therapy may present intermittent viremia (blip); however, predictors of this outcome and its influence on the incidence of virologic failure remain controversial in the literature. The aim of this study is to estimate the incidence of blip and virologic failure in a cohort of patients under stable antiretroviral therapy and to investigate their associated factors. Blip was defined as a plasma HIVRNA load above 50 copies/mL followed by a subsequent value below 50 copies/mL. Virologic failure was defined as two consecutives measures of viral load above 50 copies/mL. Moreover, at time of occurrence of these outcomes, HIV genotyping assays were performed in search of drug resistance-associated mutations, and plasma concentrations of nonnucleoside reverse transcriptase and protease inhibitors assessed and compared with self-reported adhrence to therapy. METHODS: 350 subjects (250 male and 100 female) were enrolled at the HIV Clinic, School of Medicine, University of São Paulo, Brazil and followed for 78 weeks. At baseline and in 3-month interval follow-up visits we collected sociodemographic data and information on presumed mode of HIV acquisition, use of and adherence to antiretrovirals, comorbidities and use of alcohol and illicit drugs. Additionally, patients were questioned about potential predictors of the outcomes, including occurrence of other diseases, immunizations and risky sexual behavior. Blood samples were drawn for assessment of HIV plasma viral loads, using ultrasensitive RT-PCR, and T CD4+ cell counts by flow cytometry. Individuals who presented blip and/or virologic failure were submitted to HIV genotyping assays and assessment of antiretroviral plasma concentrations by high-performance liquid chromatography. Incidences of blip and virological failure were estimated and associated factors investigated, using a multiple logistic regression model. RESULTS: The incidence of blip and of virologic failure were 9.4/100 and 4.2/100 person-years, respectively. Three individuals presented virologic failure after blip episodes. On multivariate analysis, non-adherence to safer sex measures in the previous month was shown independently associated with the occurrence of blip (OR 24.64, 95%CI 4.40 137.88, p<0.001) and virologic failure (OR 24.69, 95%CI 4.20 145.18, p<0.001). In addition, history of multiple exposures to antiretroviral regimens was also a predictor of blip (OR 1.82, 95%CI 1.41 2.36, p<0.001) and virologic failure (OR 1.67, 95%CI 1.19 2.35, p<0.001). Blips were not predictive of virologic failure. A larger number of HIV mutations were identified at time of virologic failure, as compared to blip episodes, with mutations detected predominantly in the reverse transcriptase (RT) gene, probably due to larger exposure to RT inhibitors. Eighty-four out of 122 assessments of antiretroviral plasma concentrations analyzed in 120 samples resulted in the therapeutic range. However, these results were concordant with self-reported adherence to therapy in 69% of cases only. This study shows that a single blip episode may be considered benign, whereas virologic failure could result from accumulation of HIV drug resistance-associated mutations that may impair the efficacy of therapy. Both study outcomes occurred more frequently among patients with larger exposure to antiretrovirals, and therefore they should be monitored in this regard. An important contribution of this study concerns the assessment of antiretroviral plasma concentrations, a simple and low cost laboratory tool. Incorporated routinely in patient follow-up, it would help monitoring adherence to therapy and reduce the need for HIV genotyping assays

Magister Public Health - MPH / Aim: This study aimed to evaluate the effectiveness of the Mobile HIV/AIDS Treatment Teams in initiating and treating patients with HAART at fixed primary health care clinics Amajuba District.

Orientador: Helaine Maria Besteti Pires Mayer Milanez / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T14:20:51Z (GMT). No. of bitstreams: 1 PinhoNeto_OtavioSoares_D.pdf: 1689484 bytes, checksum: 9ac072f9702d3565268cb5bc1930d222 (MD5) Previous issue date: 2014 / Resumo: OBJETIVO: Analisar os protocolos de Antirretrovirais em uma coorte de gestantes HIV positivas e recém-natos expostos em seguimento no Serviço de Assistência Especializada (SAE) Familiar/Hospital Universitário Lauro Wanderley (HULW)/Universidade Federal da Paraíba (UFPB) no período de 2005 a 2012. SUJEITOS E MÉTODOS: Estudo descritivo, do tipo coorte, retrospectivo, numa abordagem quantitativa, a partir de um grupo de gestantes HIV+ e seus recém-nascidos (RN) expostos, atendidas no SAE Familiar do HULW/UFPB. Os dados foram codificados, digitados e armazenados em um banco de dados criado com esse propósito. Cada par mãe-RN foi identificado com um número. Foi realizada uma análise descritiva das características sociodemográficas da gestante, do acompanhamento pré-natal, do uso de terapia antirretroviral (TARV), do parto e do recém-nascido, através de distribuição percentual ou média. Posteriormente, foi realizada a análise das classes dos antirretrovirais e seus desfechos para a mãe e recém-nascidos expostos. As possíveis associações entre as variáveis categóricas foram testadas através do teste t (dados paramétricos). Não foi possível a realização de análise multivariada devido ao pequeno número de crianças infectadas. RESULTADOS: A taxa de transmissão vertical (TV) no SAE Familiar HULW/UFPB entre 2005 e 2012 foi de 3,9% em uma coorte de 153 gestações analisadas. A média de idade das gestantes foi de 25 anos e a de escolaridade de 7 anos. A maioria era de mulheres negras (78,7%), com união estável (59%), e a principal categoria de exposição foi a sexual (96,5%). Mais de cinquenta por cento já apresentavam diagnóstico do HIV anterior à gravidez estando 41% em uso de TARV. A média de CD4 inicial foi de 440 células/ml e, após uso de TARV de 516,07 células/ml. A média de carga viral (CV) pré uso de TARV foi de 24.022. Mais de 70% apresentaram carga viral indetectável com 34 semanas de gestação. Usaram TARV com IP 92% e 8% um esquema com nevirapina. Não foi utilizada monoterapia com AZT nessa coorte. A média de idade gestacional no parto foi de 36 semanas e em 95% dos casos a via de parto foi cesárea. A grande maioria dos casos (98%) recebeu AZT endovenoso no parto. O peso médio dos recém-nascidos foi de 2,89 gramas e apenas 17,64% tiveram baixo peso. A presença de prematuridade, patologias neonatais e o não uso do AZT intraparto foram fatores que se associaram a um maior risco de transmissão vertical. Não foi possível a realização de análise multivariada devido ao pequeno número de crianças infectadas. Houve poucos efeitos colaterais associados ao uso da TARV na gestação, sendo o mais frequente a presença de anemia materna (58,4%) e de anemia neonatal (21,6%). Não se observaram efeitos adversos graves, tanto na mãe quanto no recém-nascido. CONCLUSÃO: A taxa de TV no serviço universitário de João Pessoa foi de 3,9%, principalmente associada à prematuridade, patologia neonatal e não uso do AZT venoso intraparto. Houve baixa ocorrência de efeitos adversos, sendo mais frequente a anemia, tanto na mãe quanto no recém-nascido / Abstract: OBJECTIVE: To analyze antiretroviral therapy protocols in a cohort of HIV-positive pregnant women and exposed newborns followed at Serviço de Assistência Especializada (SAE) Familiar / Hospital Universitário Lauro Wanderley (HULW), Universidade Federal da Paraíba (UFPB), from 2005 to 2012. SUBJECTS AND METHODS: Descriptive, retrospective cohort study, using a quantitative approach, conducted on a group of HIV-positive pregnant women and their exposed newborns followed at SAE/HULW. Data were codified, entered and stored in a database created specifically for this purpose. Each mother-child pair was identified by a number. A descriptive analysis of the sociodemographic characteristics of pregnant women, prenatal care, use of antiretroviral therapy (ART), and delivery and neonate parameters was conducted using percentages or means. An analysis of the classes of antiretroviral drugs and their associated outcomes for mothers and exposed newborns was then conducted. Potential associations between categorical variables were assessed with the t-test (parametric data). Multivariate analysis could not be performed due to the small number of children infected. RESULTS: The mother-to-child transmission rate at SAE/HULW-UFPB between 2005 and 2012 was 3.9%, in a cohort of 153 pregnancies. The mean patient age was 25 years and the mean educational attainment was 7 years of schooling. Most subjects were black women (78.7%), in a stable relationship (59%), and the main risk factor was sexual contact (96.5%). More than 50% already had a diagnosis of HIV infection prior to pregnancy, and 41% were on ART. The mean CD4 count was 440 cells/ml at baseline and 516.07 cells/ml after ART. The median viral load before ART was 24.022. Over 70% had an undetectable viral load at 34 weeks of gestation. Overall, 92% were on PI-containing ART regimens and 8% were on nevirapine-containing regimens. AZT monotherapy was not used in this cohort. The mean gestational age at delivery was 36 weeks, and in 95% of cases, the mode of delivery was cesarean. The vast majority of cases (98%) received intrapartum intravenous AZT. The average birth weight of newborns was 2,890 g, and only 17.6% were underweight. Presence of prematurity, neonatal morbidity, and failure to administer intrapartum AZT were factors associated with higher risk of vertical transmission. Multivariate analysis could not be performed due to the small number of infected children. There was a low incidence of side effects associated with ART during pregnancy, the most common being maternal anemia (58.4%) and neonatal anemia (21.6%). No serious adverse effects were observed in either mothers or newborns. CONCLUSION: The rate of mother-to-child transmission at this university-based facility in João Pessoa was 3.9%, and was mainly associated with prematurity, neonatal morbidity, and failure to administer intrapartum intravenous AZT. There was a low rate of adverse effects, the most common being anemia, in both mothers and newborns / Doutorado / Saúde Materna e Perinatal / Doutor em Ciências da Saúde

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Background: Despite the effort of scientific research on HIV therapies and to reduce the rate of HIV infection, AIDS remains one of the major causes of death in the world and mostly in sub-Saharan Africa. To date, neither a cure nor an HIV vaccine had been found and the disease can only be managed by using High Active Antiretroviral Therapy (HAART) if detected early. The need for an effective early diagnostic and non-toxic treatment has brought about the necessity for the discovery of additional HIV diagnostic methods and treatment regimens to lower mortality rates. Antimicrobial Peptides (AMPs) are components of the first line of defense of prokaryotes and eukaryotes and have been proven to be promising therapeutic agents against HIV. Methods: With the utility of computational biology, this work proposes the use of profile search methods combined with structural modeling to identify putative AMPs with diagnostic and anti-HIV activity. Firstly, experimentally validated anti-HIV AMPs were retrieved from various publicly available AMP databases, APD, CAMP, Bactibase and UniProtKB and classified according to super-families. Hidden Markov Model (HMMER) and Gap Local Alignment of Motifs (GLAM2) profiles were built for each super-family of anti- HIV AMPs. Putative anti-HIV AMPs were identified after scanning genome sequence databases using the trained models, retrieved AMPs, and ranked based on their E-values. The 3-D structures of the 10 peptides that were ranked highest were predicted using 1-TASSER. These peptides were docked against various HIV proteins using PatchDock and putative AMPs showing the highest affinity and having the correct orientation to the HIV -1 proteins gp120 and p24 were selected for future work to establish their function in HIV therapy and diagnosis. Results: The results of the in silica analysis showed that the constructed models using the HMMER algorithm had better performances compare to that of the models built by the GLAM2 algorithm. Furthermore, the former tool has a better statistical and probability explanation compared to the latter tool. Thus only the HMMER scanning results were considered for further study. Out of 1059 species scanned by the HMMER models, 30 putative anti-HIV AMPs were identified from genome scans with the family-specific profile models after the elimination of duplicate peptides. Docking analysis of putative AMPs against HIV proteins showed that from the 10 best performing anti-HIV AMPs with the highest E-scores, molecules 1,3, 8, and 10 firmly bind the gp120 binding pocket at the VIN2 domain and the point of interaction between gp120 and T cells, with the 1st and 3rd highest scoring anti-HIV AMPs having the highest binding affinities. However, all 10 putative anti-HIV AMPs bind to the N-terminal domain of p24 with large surface interaction, rather than the C-terminal. Conclusion: The in silica approach has made it possible to construct computational models having high performances, and which enabled the identification of putative anti-HIV peptides from genome sequence scans. The in silica validation of these putative peptides through docking studies has shown that some of these AMPs may be involved in HIV/AIDS therapeutics and diagnostics. The molecular validation of these findings will be the way forward for the development of an early diagnostic tool and as a consequence initiate early treatment. This will prevent the invasion of the immune system by blocking the VIN2 domain and thus designing of a successful vaccine with broad neutralizing activity against this domain.

PhDH / Department of Public Health / Background: Since the introduction of three-tiered systems appointments, there are a large number of missed appointments among Human immunodeficiency virus-positive clients on Antiretroviral. However, no one knows why these clients missed their scheduled times. Missing of appointments predicts poor adherence and is associated with poor clinical outcomes. Objectives: The proposed study aimed at developing a strategy for reducing the missing of appointments among adults on Antiretroviral Therapy in the Limpopo Province, South Africa. The objectives of the study are to determine patients’ behaviour, the socio-environmental and economic factors that contribute to the missing of appointments and develop strategies to enhance compliance with appointments by Human immunodeficiency virus-positive clients on Antiretroviral therapy in the Limpopo Province. Method: A qualitative research design was used to address the study objectives. Non-probability purposive sampling was used to sample health care centres in Limpopo Province, patients, Professional Nurses and Community Health Workers. Individual interview and focus group discussions strengthened the triangulation of data obtained from the participants. Creswell’s model provided details for data analysis and interpretation. Trustworthiness and Ethics: Measures to ensure data quality, such as credibility, dependability, conformability and transferability, were observed. The researcher ensured compliance with ethical standards to protect the rights of the participants. Approval for this study was obtained from the University of Venda Research Ethics Committee and the Limpopo Department of Health Research Ethics. Results: The study revealed various factors that contribute to the missing of appointments by Human immunodeficiency virus positive-clients on Antiretroviral Therapy. Specific socioeconomic, behavioural, environmental and health service-related factors appear to prevent adherence to appointments. These factors include a lack of family support and client engagement, the absence of financial means, and cultural and religious beliefs. Lack of client involvement in planning their care and poor referral of clients to community health workers were ranked high as being the most contributing factors to clients missing their appointments. Strategy development: Phase 2 of this study dealt with the development of the strategy aimed at reducing the missing of appointment by adults on Antiretroviral Therapy based on the findings of the study. The strengths, weaknesses, opportunities and threats matrix was triangulated in Political, Environmental, Social, Technological and Legal analysis to develop this approach to reduce the missing of appointments among adults on Antiretroviral therapy. A transtheoretical framework illustrated how to implement the strategy. Validation of the developed strategy ensured that the system is free of errors and checked the applicability of the strategies utilising a quantitative design. A simple random sampling approach was used to select the population to participate in this study using the questionnaire developed by the researcher. Almost all respondents agreed that the strategy would facilitate reduced missing appointments by adults on Antiretroviral therapy. Recommendations: Clients involvement and engagement throughout the process of a treatment plan is essential to identify some of the barriers that might contribute to poor adherence to appointment by clients on Antiretroviral therapy. Community health workers and nurses should be capacitated with knowledge and skills to identify the clients at risk of defaulting treatment and appointments and provide counselling that will facilitate behaviour modifications. / HWSETA

Purpose: The purpose of this study is to assess risk factors associated with TB co-infection in HIV/AIDS patients taking antiretroviral therapy (ART). Methodology: An observational, analytic, case-control and quantitative study was conducted on a randomly selected 367 HIV and AIDS patients of whom 92 of them were TB co-infected. Data collection was done by using self-structured questionnaire. Result: In this study, educational status, waste disposal system, monthly income, contact history with a patient of active tuberculosis or presence of a family member with active tuberculosis, drug adherence, knowledge on tuberculosis prevention and history of exposure to substance were factors independently associated with the occurrence of active tuberculosis among HIV and Aids patients taking ART. Conclusion: The findings highlight the need for on-going educational, informational and other interventions to address the risk factors of tuberculosis in HIV and Aids patients in order to decrease the rate of TB co-infection / Health Studies / M.A. Public Health