Human Endogenous Retroviruses (HERV) are segments of the human genome that are viral in origin and occupy approximately 8% of the human genome, which is nearly 3 times as much as functional protein coding genes (3%). Although most are defective due to accumulation of post insertional mutations, Human Endogenous Retrovirus Type K (HERV-K) retains the ability to produce functional particles and is activated during progression of malignant disease. The resulting proviral products have been associated tumorigenesis through their presumed role in malignant cell production. While therapeutics that focus on HERV-K inhibition have not been manufactured, current Federal Drug Administration (FDA) approved antiretroviral therapies are capable of decreasing expression of HERV-K in cancer cells. In summary, antiretroviral drugs may serve as a promising new anticancer drug by targeting and decreasing expression of HERV-K proteins.

Made available in DSpace on 2014-06-11T19:31:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-25Bitstream added on 2014-06-13T20:02:02Z : No. of bitstreams: 1 geraix_j_dr_botfm.pdf: 538830 bytes, checksum: a76b460005466efa7d2941012c34da2d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / O advento da utilização da terapia antiretroviral de alta atividade (HAART), a partir de 1996, representou um profundo impacto na história natural da infecção pelo HIV, promovendo uma importante e sustentada supressão na replicação viral, elevando a sobrevida e a qualidade de vida dos pacientes soropositivos. No entanto, gradualmente, foi se observando que a terapia antiretroviral é acompanhada de alterações metabólicas, como dislipidemia, principalmente hipertrigliceridemia, resistência insulínica, hiperglicemia e lipodistrofia, isto é, redistribuição da gordura corporal. Ensaios epidemiológicos demonstram correlação entre os níveis elevados de triglicerídeos (TG) e maior incidência de doença arterial coronariana (DAC). Autores sugerem a intervenção dietética como parte do tratamento da hiperlipidemia, incluindo aumento da ingestão de fibra solúvel (10g-25g/dia). Há estudos demonstrando que tanto o colesterol quanto os triglicerídeos séricos diminuem com a utilização de fibra alimentar. Alguns observaram redução apenas nos níveis séricos de triglicerídeos, enquanto que outros não verificaram alteração no metabolismo lipídico. O objetivo do presente estudo foi avaliar o efeito da fibra solúvel (goma guar parcialmente hidrolisada) suplementar sobre a hipertrigliceridemia e o perfil imunológico de indivíduos HIV positivo em tratamento com HAART. Foram estudados 19 pacientes HIV positivo com hipertrigliceridemia (níveis séricos ³ 150 a < 500mg/dL), sendo 63,16% do sexo masculino e 36,84% feminino, com média de idade de 43,52 ± 9,22 anos. Esses indivíduos utilizavam o mesmo esquema HAART há pelo menos seis meses, sem mudança da terapia durante o estudo e receberam 20g de fibra solúvel por dia, durante quatro meses... / The advent of highly active antiretroviral therapy (HAART), since 1996, represented a profound impact on the natural history of HIV-infection by promoting important and sustainable viral replication suppression and increasing survival and quality of life among seropositive patients. Nonetheless, antiretroviral therapy has been observed to be accompanied by metabolic alterations such as dyslipidemia, especially hypertriglyceridemia, insulin resistance, hyperglycemia and lipodystrophy (body fat redistribution). Epidemiological studies have demonstrated a correlation between high triglyceride (TG) levels and higher incidence of coronary artery disease (CAD). Some investigators suggest dietary intervention as part of hyperlipidemia treatment, including an increase in soluble fiber intake (10-25g/day). Whereas some studies have demonstrated that both cholesterol and serum triglyceride levels decrease with the use of food fiber, others have shown just a serum triglyceride decrease, and others failed to observe any alteration in lipid metabolism. The purpose of this study was to assess the effect of soluble fiber® (partially hydrolyzed guar gum) supplementation on hypertriglyceridemia and immune profile in HIV-positive individuals on HAART. Nineteen HIV-positive individuals with hypertriglyceridemia (serum levels 150 to < 500 mg/dL) were studied. Of these individuals, 63,16% were males and 36,84% females, with mean age of 43,52 ± 9,22 years. These individuals had been on the same HAART regimen for at least 6 months, had no change in therapy during the study and received 20g/day of soluble fiber for four months at pre-established times. Clinical-nutritional, biochemical (total proteins, albumin, globulin, total cholesterol, LDL-c, HDL-c, TG, TG/HDL-c and LDL-c/HDL-c)... (Complete abstract click electronic access below)

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.

Magister Public Health - MPH / Background: Early HIV testing is a crucial step for pregnant women in preventing mother-to-child transmission of HIV. In the public sector nearly all pregnant women presenting at antenatal clinics are screened for HIV. However, according to a large medical-aid administrator in South Africa, only 21.96% of pregnant women on their medical aid claimed for an HIV test as part of their antenatal care in 2012. Despite having frequent opportunities when consulting with pregnant women, general practitioners tend to be reluctant to offer HIV screening to these privately insured patients. In South Africa, private sector general practitioners are reimbursed for their services at pre-determined, negotiated rates. Previous studies indicate that monetary incentives over and above the negotiated rate may motivate health providers to promote screening to patients, and this may lead to increases in the uptake of testing. Due to limited resources within the public health sector, general practitioners are seen as key resources in a public private partnership to assist government achieve strategic health outcomes such as improved access to quality healthcare and improved compliance to treatment plans. Methodology: A quasi-experimental, ‘before and after’ study design, was conducted among 2,934 Metropolitan Health network general practitioners in South Africa who managed a pregnant woman on a medical aid. The same populations of general practitioners were used in the pre and post analysis with the general practitioners receiving information about the benefits of HIV testing in pregnant women before and after. The only difference was with the intervention related to a new HIV Counselling and Testing incentive process. Data was extracted from the billing system of a private medical insurance company in South Africa>. Quantitative data and stratification was analysed using the Statistical Package for the Social Science software, version 16.0 and Epi Info version 7.1.0.6. The effectiveness of the intervention was assessed by comparing the pre intervention period between April 2011 and September 2012, and post intervention period between March 2013 and August 2014. A subgroup analysis was done to determine variations in the name it, by general practitioners and patient characteristics. Results: There was no significant difference in HIV testing by general practitioners in this network preand post the intervention (21.99% vs. 21.96%, p=0.939). Compared to general practitioners aged 25-44 years, general practitioners older than 65 years old were 13% less likely to test (OR 0.87, CI: 0.74-1.01) and general practitioners between 45 and 65 years were 9% less likely to do an HIV test (OR 0.91, CI: 0.85-0.98). This study found that as patients’ age increased, they were more likely to be tested: beneficiaries aged 35- 44 years were 15% more likely to be tested compared to beneficiaries aged 15-24 years (OR 1.15, CI: 1.1-1.21). Beneficiaries who had a vaginal delivery were less likely to be tested compared to women who chose caesarean as a delivery method (OR 0.87, CI: 0.84-0.9). Medium income beneficiaries were more likely to be tested compared to low income beneficiaries (OR 1.09 CI: 1.03-1.16) and beneficiaries from the “high income” scheme grouping were less likely to be tested (OR 0.87, CI: 0.82-0.92) compared to the low income scheme grouping. The timing and frequency rates of HIV testing, for both caesarean and vaginal deliveries, occurred most between months two and six, peaking at month four. Overall, Eastern Cape and Mpumalanga had the lowest testing rates compared to all the other provinces (OR 0.96 CI: 0.89-1.05). Conclusions: Most general practitioners’ HIV testing rates of pregnant women in the private sector behaviour analysed in this study remained the same, despite the presence of a financial incentive. This study’s findings suggest that healthcare provider behaviour to comply with clinical guidelines and best practice, has no association with the presence of financial incentives, especially with increased administration tasks to access the incentive. These study findings emphasise the need to continue to strive for improved compliance especially by older general practitioners’ to adhere to clinical best practice and national HIV screening guidelines of pregnant women. The aspiration of achieving the highest quality of care in both private and public sector are principles that should continue to be pursued especially where private sector general practitioners’ will be used to offer public health services in the future National Health Insurance.

Magister Pharmaceuticae - MPharm / Access to antiretroviral therapy (ART) for HIV positive patients has brought hope and a chance to a healthier longer life with improved quality of life (QoL). In this study we explored the difference in health related quality of life (HRQoL) between participants eligible for ART and those not yet eligible for ART as per the 2015 South African HIV treatment guidelines. We also considered the impact of ART access on HRQoL and the effect of employment status and education level. The study was conducted at one tertiary hospital and two primary health care facilities in Johannesburg, South Africa.

Magister Public Health - MPH / The government of Namibia established a comprehensive HIV/AIDS treatment and care programme in 2002. This programme provides anti-retroviral treatment to all eligible HIV patients in the public health sector. The antiretroviral treatment programme in Keetmanshoop started in October 2003. Adherence to treatment regimes in HIV care is a key factor in determining clinical outcomes and is associated with improved survival among HIV and AIDS patients. Sustained high levels of adherence (95% or more) are essential for the success of highly active antiretroviral therapy (HAART). Maintaining high adherence levels is therefore a major concern in HIV/AIDS treatment programmes. This study investigated adherence to HAART among patients in the Keetmanshoop antiretroviral therapy (ART)clinic and the factors that affect adherence.Aim of the research The aim of the research was to describe adherence to HAART and factors influencing adherence among patients in Keetmanshoop ART clinic, Namibia.Objectives: 1. To describe levels of adherence to HAART amongst clients at Keetmanshoop ART clinic. 2. To assess the changes in CD4 count and body weight of clients on HAART over a 12 month period.3. To assess factors associated with adherence to HAART.4. To analyse associations between CD4 count and adherence. 5. To analyse associations between changes in body weight and adherence. Methodology: A quantitative descriptive cross-sectional survey was used. The study population included all clients 18 years and above, who were on HAART for one year or more at the Keetmanshoop clinic. One hundred and six clients participated in the study. Data was collected through an interview with the participants and a review of clinical records. Results: Most respondents had good adherence levels; with 86.1% reporting optimal adherence levels.The respondents also showed an increase of median CD4 counts from 126 cells/μl at baseline to 304 cells/μl at 12 months and an increase in body weight from an average of 50kg at baseline to an average of 57kg at 12 months. Adherence levels were found to have an impact on CD4 cell counts and on body weight, with respondents who had sub-optimal adherence experiencing a drop in median CD4 cell counts and median body weight by 12 months.Living far from the clinic (>10km) was found to be the only factor significantly associated with sub-optimal adherence.Conclusion: The study showed a positive correlation between adherence levels and CD4 cell counts and body weight gain. In the absence of viral load, CD4 cell count testing can be used as a measure of adherence. Though most respondents appear to be adhering well to HAART, a sub-optimal adherence rate of >10% is a concern for the Keetmanshoop ART programme and will need to be addressed. There is a need for further research to determine the level of default or attrition from HAART in the programme

Magister Pharmaceuticae - MPharm / South Africa faces a huge Human Immunodeficiency Virus (HIV) burden with more than 400,000 children currently on antiretroviral therapy (ART). Studies on lipid and haematological profile changes in paediatrics are of particular interest since these children are exposed to ART in the course of a developmentally significant period and will possibly have longer collective exposure to ART. As such, monitoring for adverse effects, including lipid and haematological abnormalities, is essential for curtailing morbidity and mortality rates of children on ART. There is a dearth of studies assessing lipid and haematological abnormalities in the South African paediatric population on ART where genetic differences, co-morbidities, malnutrition and use of traditional medicines, all influence the safety profile of a drug. The goal of this study was twofold: Firstly to identify a suitable parameter for assessing lipid and haematological abnormalities in paediatrics on Antiretroviral (ARV) treatment using available secondary data and secondly, to assess prescriber adherence to routine monitoring tests in the ART guidelines. This study was a retrospective review of secondary data obtained from 168 patient clinical records at a Community Health Centre in the Cape Metropole, Western Cape and corresponding laboratory data from the National Health Laboratory Service (NHLS) database. Appropriate cholesterol, triglyceride, haemoglobin and neutrophil test results were compared against the standard reference ranges/values. The Chi-Squared test identified associations between total cholesterol (TC) /triglycerides and haemoglobin (Hb)/neutrophil and other independent variables. Evaluation of health care provider adherence to routine monitoring tests was assessed against relevant national ARV management guidelines. There was a paucity of baseline data for all laboratory markers and infrequent follow-up tests were ordered by healthcare providers. This precluded the measurement of changing lipid and haematological levels and an alternative parameter, viz., the highest available laboratory test value for each marker per patient, was assessed against reference values/ranges. Only nine out of the 36 (25%) patients on an AZT regimen had any Hb or neutrophil laboratory tests performed and 23 and two out of 97 (24% and 2%) patients, respectively, on a protease inhibitor (PI) had a TC and triglyceride laboratory test performed. Anaemia was detected in 45.5 % of children below five years of age, in 21.7% between ages of six and 11 and in 65.5 % between 12 and 14 years of age. Neutropenia was detected in 25.6% of children below five years of age and in 50% aged between six and 11. Hypercholesterolemia was found in 13.1% of patients. The only statistically statistical associations were found between the TC and CD4 count in children aged six to 14 years (χ2=5.000; p=0.025) and between neutrophil counts and viral load in children aged six to 14 years (χ2=6.4532; p=0.0240). A significant association was also found between Hb levels and viral load (χ2=7.000; p=0.008). In the absence of baseline test results and routine monitoring of haematological and lipid profiles, this study presents a potential alternative marker for assessing lipid and haematological abnormalities using the highest level of neutrophil, Hb, TC and triglycerides recorded for each patient.

Magister Public Health - MPH / Background: Even though there have been marked increases in the number of patients accessing HIV care and treatment in sub-Saharan Africa, challenges in patient retention remain. Most health systems in sub-Saharan Africa routinely report on loss to follow up of patients, but only a limited number of factors associated with loss to follow up are measured. In Kenya there is limited research on loss to follow up in HIV care and treatment programs. This study reports on rates of loss to follow up and factors associated with loss to follow up at the New NyanzaProvincial General Hospital (NNPGH) in Kisumu, Kenya. Methods: A retrospective cohort study of 4,740 adult patients that was registered for HIV and AIDS care and treatment between 2003 and 2008 was conducted. Data was analysed using SAS 9.2 and STATA 10. Cox proportional hazard ratio was calculated to describe the association between risk factors and loss to follow up. Results of the total 4740 patients, 64.6% were female, males [median age of 36 (IQR 30-44) years vs. 32 (IQR 26-39) years for females] were older than females, more males (68.3%) were married, more females (6.2%) had no education and 68% of all patients enrolled had been lost to follow up over 6 years. Risk for lost to follow up was greater amongst males (Adjusted Hazard Ratio (AHR) =1.12; 95% Confidence Interval (CI) = 1.02-1.22); younger patients(15-30 vs. >40 years: AHR=1.37, 95%CI = 1.23 – 1.53; and 31-40 vs. >40 years: AHR=1.15, 95%CI=1.03-1.28); those who were unemployed (AHR=1.14, 95%CI=1.05-1.25); and having advanced HIV disease (WHO stage 4 vs. WHO stage 1: AHR=1.53, 95%CI=1.29-1.81). Patients on ART (AHR=0.64, 95%CI=0.52-0.78) at enrollment were less likely to be lost to follow-up compared to those in HIV care. Conclusion: More attention is needed in developing retention strategies for patients with much focus on patients on care. Targeted intervention is required to improve retention amongst males, unemployed patients, patients with advanced HIV disease and younger patients. Additionally, targeted follow up in the community for patients on care is required.

Magister Public Health - MPH / Background: Adherence of patients on antiretroviral therapy to lifelong treatment is a major challenge within the public health system in Namibia. Missed appointments have been shown to contribute to poor clinical outcomes and treatment failure, which may necessitate switching to more expensive antiretroviral regimens. In resource limited settings monitoring of appointments for antiretroviral medication pick up is a documented and feasible method for assessing minimum levels of adherence to antiretroviral medication. Aim: This study was aimed at evaluating the effects of telephonic short message service reminders influence on adherence to scheduled antiretroviral medication pick up appointments. It was also aimed at evaluating how socio-demographic parameters might moderate the effectiveness of short message service reminders. Study design: A randomized double blind controlled study design was employed. Methodology: Stable patients attending the ART clinic were recruited and randomly assigned to either an intervention or control group, until the sample size of 398 was reached in the two arms of the study. The study populations were adult patients’ ≥ 18 years who have been enrolled on treatment for ≥ 3months. The intervention group received an unasked for single short message service reminder, sent 48 hours before their scheduled appointments and continued with standard care, while the control group received standard care without any reminder. The study participants were blinded to their study group. Also, research assistants involved in collecting baseline and outcome data were blinded to study participants study group. Baseline data was collected through a structured questionnaire. Study participants were followed up for four consecutive scheduled ARV pick up appointments. The following outcome data were collected at each follow up visit; number of days late after scheduled appointment, adherence measured by pill count and 3 days self-report recall of adherence. Main results: The pre-intervention survey revealed that only 60% of the study participants were willing to be reminded of their medication pick up appointment. Overall, the SMS reminder improved adherence to medication pick up appointments by 1.6 times as compared to no reminder and also reduced the risk of missing medication pick appointments by 22% as compared to no SMS reminder. Study participants that received a reminder were also two times more likely to achieve optimal adherence to their medication, compared to those who received no reminder. The SMS reminder improved adherence to antiretroviral medication by 11% in this study, while the mean difference in the number of days late to collect antiretroviral medication was significantly reduced by about 4 days by the intervention. Participants that are employed were more likely to adhere to antiretroviral medications as compared to the unemployed. Ironically participants that were on ART for less than one year and those that had treatment supporters reminding them of their medication appointments were significantly less likely to honour their medication pick up appointments. Conclusion: Being employed was significantly associated with attaining optimal adherence to antiretroviral medication. There were no other significant associations between the patients socio- economic and demographic characteristics and adherence to scheduled medication pick up appointments, or to adherence to medication. Recommendations: The Ministry of Health and Social Services should consider rolling out SMS reminders to ART sites with similar settings as Swakopmund State Hospital ART Clinic. Patients that are willing to receive the reminder should be targeted in the scaling up of the roll out. Late and missed medication pick up appointments could be used as an easy proxy measurement for assessing adherence to ART.

Magister Artium (Social Work) - MA(SW) / Botswana is experiencing high levels of HIV prevalence rate at 16.9% among the general population, 4.5% among adolescents aged 10-14 and 4.7% among adolescents aged 14-19. Adolescents are in a critically stage between childhood and adulthood and undergo a lot of developmental changes physically, sychologically and emotionally. The scourge of HIV/AIDS has also brought with it multiple challenges to adolescents as those who are HIV positive have to adhere to all the health requirements of being HIV positive and at the same time being pressurised by the societal expectations. Stigmatisation and discrimination are experienced as barriers against the fight towards HIV which is seen a major factor among adolescents. The aim of the study was to explore and describe adolescents’ perceptions and experiences of anti-retroviral therapy at a tertiary hospital in Francistown, Botswana. The study followed a qualitative research approach with an exploratory descriptive research design. Purposive sampling was used to recruit participants. Participants were school going adolescents aged between 13 and 19 years, who are on antiretroviral therapy and going for reviews at a tertiary hospital in Francistown, Botswana. Data were gathered though face to face semi structured interviews with each of the 24 participants. Data were analysed thematically. The following four themes emerged during the analysis: i. “ARVs control but don’t cure”; ii. “Why did it happen to me?-the reality of using ARVs”; iii. “I don’t want to take them for the rest of my life”; and iv. “No man is an island”, which addressed the research objectives. The findings led to the conclusion that, despite the fact that HIV has been around for over two decades and ARVs has been around for more than a decade, adolescents living with HIV still faces challenges such as stigmatisation due to social as well as clinical factors and adjusting to a lifelong treatment which made it difficult for them to adhere to their treatment. However, adolescents are happy as they are living a healthy and a fruitful life as a result of the ARVs. Ethical considerations were adhered too. Furthermore the findings of the study could assist the Ministries of Health, Education, Local Government and Rural Development to address these challenges experienced by the adolescents in the development of social programmes to improve the livelihood of the adolescents living with HIV/AIDS.